TY - JOUR. T1 - Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimers disease cases. AU - OBryant, Sid E.. AU - Hobson, Valerie L.. AU - Hall, James R.. AU - Barber, Robert C.. AU - Zhang, Song. AU - Johnson, Leigh. AU - Diaz-Arrastia, Ramon. PY - 2011/1. Y1 - 2011/1. N2 - Aims: Our purpose was to study the link between serum brain-derived neurotrophic factor (BDNF) levels and neuropsychological functioning through the Texas Alzheimers Research Consortium cohort. Methods: A total of 399 participants [probable Alzheimers disease (AD) n = 198, controls n = 201] were available for analysis. The BDNF levels were assayed via multiplex immunoassay. Regression analyses were utilized to examine the relation between BDNF levels and neuropsychological functioning. Results: There were no significant mean differences in BDNF levels between cases and controls. In the AD group, the BDNF levels were significantly negatively associated with the ...

TY - JOUR. T1 - Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons. AU - Tarsa, L.. AU - Bałkowiec-Iskra, E.. AU - Kratochvil, F. J.. AU - Jenkins, V. K.. AU - McLean, A.. AU - Brown, A. L.. AU - Smith, J. A.. AU - Baumgartner, J. C.. AU - Balkowiec, A.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2010/6. Y1 - 2010/6. N2 - Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by ...

Researchers have reported that serum brain-derived neurotrophic factor (sBDNF) of drug-free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect

TY - JOUR. T1 - Repeated electroconvulsive stimuli increase brain-derived neurotrophic factor in ACTH-treated rats. AU - Li, Bingjin. AU - Suemaru, Katsuya. AU - Cui, Ranji. AU - Kitamura, Yoshihisa. AU - Gomita, Yutaka. AU - Araki, Hiroaki. N1 - Funding Information: This work was supported in part by the Japanese Health Science Foundation and a Grant-in Aid for Scientific Research (No. 17590127) from the Japanese Ministry of Education, Science, Sports and Culture in Japan, and the Uehara Memorial Foundation.. PY - 2006/1/4. Y1 - 2006/1/4. N2 - Electroconvulsive therapy is considered to be an effective treatment for severe depression. We have already shown that the antidepressant-like effects of tricyclic antidepressants in the rat forced swim test are blocked by repeated treatment with adrenocorticotropic hormone (ACTH). In the present study, we investigated the effect of repeated electroconvulsive stimuli on the forced swim test and on brain-derived neurotrophic factor (BDNF) protein levels in ...

Experimental evidence in mice indicates that environmental conditions affect females and males differently. However, in a recent study analyzing the heterozygous mutation of brain-derived neurotrophic factor (BDNF), both sexes presented a similar emotional phenotype, which became obvious only under impoverished, but not in enriched conditions suggesting an enrichment-induced rescue. To investigate the basis of this behavioral rescue effect, we analyzed neurochemical changes (BDNF expression, serotonergic changes, and corticosterone) in the hippocampus, frontal cortex and hypothalamus of animals housed under respective conditions. In male mice, enrichment induced an increase of BDNF expression in the hippocampus of both BDNF heterozygous (BDNF(+/-)) and wild-types. Notably, in enriched-reared BDNF(+/-) mice BDNF mRNA and protein increased to levels comparable to those of wild-types in impoverished environment. In the frontal cortex of males, only wild-types presented an enrichment-induced increase of

Exercise is recognized as a promising approach to counteract aging-associated declines in cognitive functions. However, the exact molecular pathways involved remain unclear. Aerobic training interventions and improvements in peak oxygen uptake (VO2peak) have been associated with increases in the peripheral concentration of brain-derived neurotrophic factor (BDNF) and better cognitive performances. However, other training interventions such as resistance training and gross motor skills programs were also linked with improvements in cognitive functions. Thus far, few studies have compared different types of physical exercise training protocols and their impact on BDNF concentrations, especially in participants over 60 years old. The main objective of this study was to compare the effects of three exercise protocols on plasma BDNF concentrations at rest in healthy older adults. Thirty-four older adults were randomized into three interventions: (1) lower body strength and aerobic training (LBS-A), (2) upper

Fig. 6 HSP105-siRNA in HT22 cells or stressed mouse brain decreased BDNF levels and abolished antidepressant effects.. (A) Level of HSP105 mRNA in HT22 cells (ANOVA, F2,13 = 544.1, n = 5 to 6). (B) Level of BDNF mRNA in HT22 cells (ANOVA, F2,13 = 10.74, n = 5 to 6). (C) The level of HSP105 protein in the hippocampus was detected by Western blotting (n = 3). (D) Immobility times in the forced swim test (ANOVA, F2,11 = 6.03). (E) Immobility times in the tail suspension test (ANOVA, F2,11 = 15.02). (F) Social interaction rate in the interaction test (ANOVA, F2,11 = 5.00). (G) Sucrose preference and total fluid intake in the sucrose preference test. (H) Level of BDNF mRNA and protein in the mouse hippocampus (ANOVA, F2,11 = 4.54 and F2,12 = 5.41, respectively) (n = 4 to 5 animals per group). Each bar indicates the mean ± SEM. GGA + NTC, GGA with nontargeting control; GGA + HSP105-siRNA, GGA with HSP105-siRNA treatment. Statistically different groups are indicated by letters. ...

Executive Chairman and Chief Executive Officer of Minerva. In addition, the BDNF findings are paving the way to explore roluperidones therapeutic potential beyond schizophrenia.. BDNF is a member of a family of proteins called neurotrophins that play an important role in the formation and function of neural connections. An emerging body of evidence has pointed to a link between BDNF and CNS disorders. Epigenetic changes in the BDNF gene have been shown to be related to the pathophysiology of schizophrenia, and the reduced expression of BDNF has been identified in the frontal cortex and hippocampus of the brain in patients with schizophrenia.4. Researchers believe that lower than normal levels of BDNF may affect the pathogenesis of schizophrenia by contributing to altered brain development and abnormalities in neuroplasticity and synaptic function. These disturbances may explain certain morphological and neurochemical characteristics in the brains of patients with schizophrenia.5. Furthermore, ...

Brain-derived neurotrophic factor (BDNF) has neuroprotective, proangiogenic and myogenic effects and, therefore, possibly acts as a psychosomatic mediator. Here, we measured serum BDNF (seBDNF) level in hypertensive patients (HT) and healthy controls (CONT) and its relation to affective temperaments, depression and anxiety scales, and arterial stiffness parameters. In this cross-sectional study, affective temperaments, anxiety, and depression were studied with questionnaires (TEMPS-A, HAM-A, and BDI, respectively). SeBDNF level and routine laboratory parameters were measured as well. Arterial stiffness was evaluated with a tonometric method. Allover, 151 HT, and 32 CONT subjects were involved in the study. SeBDNF level was significantly higher in HT compared to CONT (24880 ± 8279 vs 21202.6 ± 6045.5 pg/mL, p | 0.05). In the final model of regression analysis, hyperthymic temperament score (Beta = 405.8, p = 0.004) and the presence of hypertension (Beta = 6121.2, p = 0.001) were independent

Background: Brain-derived neurotrophic factor (BDNF) mutant mice show hyperphagia and hyperleptinemia. Animal and cell-culture experiments suggest multiple interrelations between BDNF and the serotonin (5-HT) system. We studied serum BDNF in patients with anorexia nervosa and its associations with peripheral indicators of the 5-HT system. To control for secondary effects of acute malnutrition, we assessed acutely underweight patients with anorexia nervosa (acAN) in comparison to long-term weight-recovered patients with the disorder (recAN) and healthy controls.. Methods: We determined serum BDNF, platelet 5-HT content and platelet 5-HT uptake in 33 patients in the acAN group, 20 patients in the recAN group and 33 controls. Plasma leptin served as an indicator of malnutrition.. Results: Patients in the acAN group were aged 14-29 years and had a mean body mass index (BMI) of 14.9 (standard deviation [SD] 1.4) kg/m2. Those in the recAN group were aged 15-29 years and had a mean BMI of 20.5 (SD 1.3) ...

Open peer review is a system where authors know who the reviewers are, and the reviewers know who the authors are. If the manuscript is accepted, the named reviewer reports are published alongside the article. Pre-publication versions of the article and author comments to reviewers are available by contacting [email protected]. All previous versions of the manuscript and all author responses to the reviewers are also available.. You can find further information about the peer review system here.. ...

TY - JOUR. T1 - Loss of brain-derived neurotrophic factor-dependent neural crest-derived sensory neurons in neurotrophin-4 mutant mice. AU - Liebl, Daniel J.. AU - Klesse, Laura J.. AU - Tessarollo, Lino. AU - Wohlman, Todd. AU - Parada, Luis F.. PY - 2000/2/29. Y1 - 2000/2/29. N2 - Peripheral ganglion neurons confer sensory information including touch, pain, temperature, and proprioception. Sensory modality is linked to specific neurotrophin (NTF) requirements. NT-3 supports survival of neurons that differentiate primarily into proprioceptors whereas nerve growth factor and brain-derived neurotrophic factor (BDNF) support subpopulations that transmit nociception and mechanoreception, respectively. We examined sensory neurons of gene-targeted mouse mutants at the NT-4, BDNF, NT-3, and TrkA loci. We show that NT-4 functions early in gangliogenesis, upstream of BDNF. In the absence of NT-4 function, BDNF-dependent, TrkB-expressing neurons fail to appear. The results are consistent with the model ...

Objective It is important to predict a response to an antidepressant in early time after starting the antidepressant. We previously reported that serum brain-derived neurotrophic factor (BDNF) levels in responders to treatment with antidepressants were increased, whereas, those in nonresponders were not. Therefore, we hypothesized that the changes in serum levels of BDNF from baseline (TO) to 4 weeks (T4) after treatment with selective serotonin reuptake inhibitors (SSRIs) predict the response to the treatment at 8 weeks (T8) in depressed patients. To confirm the hypothesis, we measured serum BDNF at TO, T4, and T8 during the treatment with SSRIs (paroxetine, sertraline, and fluvoxamine). Methods One hundred fifty patients (M/F; 51/99, age; 50.4 +/- 15.1 years) met major depressive disorder (MDD) using by DSM-IV-TR enrolled in the present study. We measured serum BDNF concentrations at TO, T4, and T8 in patients with MDD treated with SSRIs. Results The changes in serum BDNF, age, sex, dose of SSRIs, and

BDNF and VEGF were analyzed as continuous variables. VEGF values were log-transformed to normalize the skewed distribution of VEGF. We used Cox-proportional hazards models to relate baseline serum BDNF and logVEGF levels (separately) to risk of incident stroke/TIA in Study Sample 1. We first examined the linear effect of a 1-SD unit increase/decrease in BDNF and logVEGF on risk of stroke/TIA. We also explored threshold effects comparing the risk across quartiles of BDNF and VEGF. We observed a threshold effect with BDNF only. Therefore, we ran threshold models for BDNF using the lowest quartile, Q1, as the reference and also assessed a threshold model comparing risk for persons in Q1 with persons in Q2 to Q4. We performed a similar set of analyses on a Study Sample 1b with stroke alone as the outcome. Using multivariable linear and logistic regression models, we examined the cross-sectional associations between BDNF and logVEGF and markers of brain aging (WMHV, and VR-d and Trails B-A ...

TY - JOUR. T1 - Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat. AU - Schmidt-Kastner, Rainald. AU - Truettner, Jessie. AU - Lin, Baowan. AU - Zhao, Weizhao. AU - Saul, Isabel. AU - Busto, Raul. AU - Ginsberg, Myron D.. N1 - Funding Information: We thank Ms Yolanda Loor for meticulous work. These studies were supported by US Public Health Service grant NS 05820.. PY - 2001/8/15. Y1 - 2001/8/15. N2 - Chronic bilateral common carotid artery occlusion (BCCAO) induces moderate ischemia (oligemia) in the rat forebrain in the absence of overt neuronal damage. In situ hybridization for brain-derived neurotrophic factor (BDNF) mRNA was used to search for a molecular response to moderate ischemia. BDNF mRNA was significantly increased in the hippocampal granule cells at 6 h of occlusion (ANOVA, Tukey test P,0.05). At 1, 7 and 14 days BDNF mRNA levels returned to ...

Objective(s): The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.Materials and Methods: The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.Results: In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone

TY - JOUR. T1 - Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder. AU - Na, Kyoung Sae. AU - Won, Eunsoo. AU - Kang, June. AU - Chang, Hun Soo. AU - Yoon, Ho-Kyoung. AU - Tae, Woo Suk. AU - Kim, Yong Ku. AU - Lee, Min-Soo. AU - Joe, Sook Haeng. AU - Kim, Hyun. AU - Ham, Byung-Joo. PY - 2016/2/15. Y1 - 2016/2/15. N2 - Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age-and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars ...

Recent epidemiological studies showed that daily coffee consumption is associated with a lower risk for several neurological disorders such as Alzheimers disease and Parkinsons disease; however, the molecular mechanisms responsible for the protective effect of coffee against neurological disorders have not been elucidated. As brain-derived neurotrophic factor (BDNF) promotes neuronal survival and protects against neuronal damage, we investigated the effects of coffee on BDNF signaling using human neuroblastoma SH-SY5Y cells. We found that brewed coffee exerted an inhibitory effect on the autophosphorylation of tropomyosin receptor kinase B (TrkB), a BDNF receptor. Additionally, coffee reduced the phosphorylation of Akt in BDNF-treated SH-SY5Y cells. Treatment with coffee did not affect the TrkB receptor on the cell surface. The major constituents of coffee, such as caffeine, caffeic acid, chlorogenic acid, and trigonelline had no effect on TrkB phosphorylation induced by BDNF. In addition, coffee

One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF) in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test). To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF). Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01), fasting glucose (r = - 0,499, p = 0.01), and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with ...

One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF) in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test). To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF). Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01), fasting glucose (r = - 0,499, p = 0.01), and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with ...

Background Following voxel-based morphometry (VBM), brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been shown to affect human brain morphology in Caucasians. However, little is known about the specific role of the Met/Met genotype on brain structure. Moreover, the relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied. Methodology/Principal Findings The present study investigated brain structural differences among three genotypes of BDNF (rs6265) for the first time in healthy young Chinese adults via cortical thickness analysis and VBM. Brain differences in Met carriers using another grouping method (combining Val/Met and Met/Met genotypes into a group of Met carriers as in most previous studies) were also investigated using VBM. Dual-approach analysis revealed less gray matter (GM) in the frontal, temporal, cingulate and insular cortices in the Met/Met group compared with the Val/Val group (corrected, P|0.05). Areas with less GM

Citation: Khundakar, A.A. and Zetterström, T.S.C. (2011) Effects of GABAB ligands alone and in combination with paroxetine on hippocampal BDNF gene expression. European Journal of Pharmacology, 671 (1-3) pp. 33-38 ...

TY - JOUR. T1 - Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. AU - Balkowiec, Agnieszka. AU - Katz, David M.. PY - 1998/7/15. Y1 - 1998/7/15. N2 - 1. Molecular mechanisms underlying maturation of the central respiratory rhythm are largely unknown. Previously, we found that brain-derived neurotrophic factor (BDNF) is required for expression of normal breathing behaviour in newborn mice, raising the possibility that maturation of central respiratory output is dependent on BDNF. 2. Respiratory activity was recorded in vitro from cervical ventral roots (C1 or C4) using the isolated brainstem-spinal cord preparation from postnatal day (P) 0.5-2.0 and P4.5 wild-type mice and mice lacking functional bdnf alleles. 3. Loss of one or both bdnf alleles resulted in an approximately 50% depression of central respiratory frequency compared with wild-type controls. In addition, respiratory cycle length variability was 214% higher in bdnf null ...

A Val66Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val66Met SNP and [15O]H2O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a key role in synaptic plasticity, in part due to changes in local protein synthesis. Activation of TrkB (tropomyosin-related kinase B) receptors for BDNF triggers several parallel signaling pathways, including the Ras/ERK, the phosphatidylinositol 3-kinase (PI3-K) and the phospholipase C-γ pathways. Recent studies have elucidated some of the signaling mechanisms that contribute to the regulation of translation activity by BDNF, through modulation of initiation and elongation phases, but the resulting changes in the proteome are not yet fully characterized. The proteins synthesized in response to activation of TrkB receptors by BDNF depend on the mRNAs that are available locally, after delivery and transport along dendrites. Recent studies have shown that BDNF may also play a regulatory role at this level. Furthermore, BDNF regulates transcription activity, thereby affecting the array of mRNAs available to be transported along dendrites.

TY - JOUR. T1 - Structure of the Brain-Derived Neurotrophic Factor/Neurotrophin 3 Heterodimer. AU - Robinson, Robert C.. AU - Stuart, David I.. AU - Jones, E. Yvonne. AU - Radziejewski, Czeslaw. PY - 1995/9/1. Y1 - 1995/9/1. N2 - The development and sustenance of specific neuronal populations in the peripheral and central nervous systems are controlled through the binding of neurotrophic factors to high-affinity cell surface receptors. The neurotrophins (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; and neurotrophin 4, NT4) are dimeric molecules which share approximately 50% sequence identity. The crystal structure of the murine NGF homodimer [McDonald et al. (1991) Nature 354, 411-414] indicated that the dimer interface corresponds to regions of high sequence conservation throughout the neurotrophin family. This potential compatibility was duly exploited for the production in vitro of noncovalent heterodimers between the different neurotrophins ...

TY - JOUR. T1 - Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites. AU - Cohen, Michael S.. AU - Orth, Carlos Bas. AU - Kim, Hyung Joon. AU - Jeon, Noo Li. AU - Jaffrey, Samie R.. PY - 2011/7/5. Y1 - 2011/7/5. N2 - Signaling from dendritic synapses to the nucleus regulates important aspects of neuronal function, including synaptic plasticity. The neurotrophin brain-derived neurotrophic factor (BDNF) can induce long-lasting strengthening of synapses in vivo and this effect is dependent on transcription. However, the mechanism of signaling to the nucleus is not well understood. Here we describe a microfluidic culture device to investigate dendrite-to-nucleus signaling. Using these microfluidic devices, we demonstrate that BDNF can act directly on dendrites to elicit an anterograde signal that induces transcription of the immediate early genes, Arc and c-Fos. Induction of Arc is dependent on dendrite- and cell body-derived calcium, whereas ...

Brain-derived neurotrophic factor (BDNF) promotes several functions in neurons and modulates neurotransmissions, especially in hippocampal regions. Frontotemporal lobar degeneration (FTLD) has a strong genetic background, but genetic risk factors ass

Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation Xin Yu,1 Laijin Lu,1 Zhigang Liu,1 Teng Yang,2 Xu Gong,1 Yubo Ning,3 Yanfang Jiang4 1Department of Hand Surgery, 2Department of Orthopedics, The First Hospital of Jilin University, Changchun, 3Department of Orthopedics, Ningshi Orthopedics Hospital of Tonghua, Tonghua, 4Department of Central Laboratory, The First Hospital of Jilin University, Changchun, Peoples Republic of China Background: Brain-derived neurotrophic factor (BDNF) has been demonstrated to play an important role in survival, differentiation, and neurite outgrowth for many types of neurons. This study was designed to identify the role of BDNF during peripheral nerve xenotransplantation. Materials and methods: A peripheral nerve xenotransplantation from rats to mice was performed. Intracellular cytokines were stained for natural killer (NK) cells, natural killer T (NKT) cells, T cells, and B cells and analyzed by flow cytometry

Brain-derived neurotrophic factor (BDNF) is a protein that is important in nervous system development and function. BDNF also appears to function downstream of the leptin-melanocortin signaling pathway to control appetite. In both animals and humans, diminished BDNF function is associated with hyperphagia, obesity, and neurocognitive deficits. We propose to study BDNF in two hyperphagic disorders: Prader-Willi syndrome and MC4R function-altering mutations. We hypothesize that patients with PWS may have increased BDNF during infancy, followed by a decline in BDNF that precedes the onset of hyperphagia and persists after the onset of obesity. We hypothesize that patients with MC4R mutations will have decreased BDNF, the severity of which will be associated with the degree of MC4R functional loss caused by the specific mutation(s) in each individual. To test these hypotheses, we wish to conduct cross-sectional studies to evaluate serum BDNF concentrations, metabolism, body composition, and ...

Context: Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide also involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD).. Objective: To investigate the association of circulating BDNF with CVD risk Design, Setting and Participants: First, we prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in the 3,687 participants (mean age 65 years, 2,068 women) from the Framingham Heart Study (FHS). Next, we evaluated the association of a common nonsynonymous SNP in the BDNF gene (rs6265) with circulating BDNF concentrations in FHS. Finally, we performed a Mendelian randomization experiment in the CARDIoGRAM consortium (,22,000 coronary artery disease [CAD] cases, ,60,000 controls) to investigate whether the same SNP was associated with CAD risk in CARDioGRAM and if so, whether the direction and effect size differed from that predicted based on ...

Author(s): Bamji, Shernaz X; Rico, Beatriz; Kimes, Nikole; Reichardt, Louis F | Abstract: Neurons of the vertebrate central nervous system have the capacity to modify synapse number, morphology, and efficacy in response to activity. Some of these functions can be attributed to activity-induced synthesis and secretion of the neurotrophin brain-derived neurotrophic factor (BDNF); however, the molecular mechanisms by which BDNF mediates these events are still not well understood. Using time-lapse confocal analysis, we show that BDNF mobilizes synaptic vesicles at existing synapses, resulting in small clusters of synaptic vesicles splitting away from synaptic sites. We demonstrate that BDNFs ability to mobilize synaptic vesicle clusters depends on the dissociation of cadherin-beta-catenin adhesion complexes that occurs after tyrosine phosphorylation of beta-catenin. Artificially maintaining cadherin-beta-catenin complexes in the presence of BDNF abolishes the BDNF-mediated enhancement of synaptic vesicle

Brain-derived neurotrophic factor (BDNF) is a protein that is important in nervous system development and function. BDNF also appears to function downstream of the leptin-melanocortin signaling pathway to control appetite. In both animals and humans, diminished BDNF function is associated with hyperphagia, obesity, and neurocognitive deficits. We propose to study BDNF in two hyperphagic disorders: Prader-Willi syndrome and MC4R function-altering mutations. We hypothesize that patients with PWS may have increased BDNF during infancy, followed by a decline in BDNF that precedes the onset of hyperphagia and persists after the onset of obesity. We hypothesize that patients with MC4R mutations will have decreased BDNF, the severity of which will be associated with the degree of MC4R functional loss caused by the specific mutation(s) in each individual. To test these hypotheses, we wish to conduct cross-sectional studies to evaluate serum BDNF concentrations, metabolism, body composition, and ...

The levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with schizophrenia and correlate with impairments in cognitive function. However, no study has investigated the relationship between the serum BDNF levels and decision-making. We compared patients with schizophrenia to healthy controls with respect to their decision-making ability and serum BDNF levels. Eighty-six chronic schizophrenia patients and 51 healthy controls participated in this study. We controlled for gender, age, and estimated intelligence quotient (IQ), and we investigated the differences in decision-making performance on the Iowa Gambling Task (IGT) between the schizophrenia patient and control groups. We also compared the IGT scores, the serum BDNF levels, and the clinical symptoms between the groups. The IGT scores of the schizophrenia patients were lower than those of the controls. A negative correlation was detected between the mean net scores on the trials in the final two blocks and the

Reduced brain-derived neurotrophic factor (BDNF) expression & secretion after treatment with advanced glycation endproducts in brain microvascular endothelial cells ...

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Figure 4. Hippocampus and Perirhinal cortex in Human Brain (Figure Source). Some studies measured serum BDNF levels instead of specifically measuring brain BDNF concentration.[21][31][32][13] Serum BDNF is measured instead of brain levels because it can be measured without sacrificing the animal and is also acceptable for human studies. Acute changes in serum BDNF levels are thought to directly reflect changes in brain BDNF concentration[21][24]. There are several reasons for this: rat studies show correlations between serum and brain BDNF levels,[21] BDNF easily travels in both directions across the blood-brain barrier,[21][24] and both serum and brain BDNF levels are significantly reduced in AD.[24] There is conflicting evidence concerning exercise and its impact on serum BDNF.[24] Acute bouts of exercise have been found to increase serum BDNF levels,[21][24] but several studies have concluded that regular (chronic) exercise may lead to decreased serum BDNF levels compared to sedentary ...

The Effects of Voluntary, Involuntary, and Forced Exercises on Brain-Derived Neurotrophic Factor and Motor Function Recovery: A Rat Brain Ischemia Model - free full-text /PMC3035657/ - Feb 2011 I was happy to find that what I have personally experienced has been proven to be true: forced exercise is not as beneficial as voluntary. Sometimes science…

Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded.

PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpressing proBDNF with either PC7 or Furin. Conversely, the processing of proBDNF into BDNF is markedly reduced in the absence of either Furin or PC7 in mouse primary hepatocytes. In vivo we observe that BDNF and PC7 mRNAs are colocalized in mouse hippocampus and amygdala and that mature BDNF protein levels are reduced in these brain areas in PC7 KO mice but not in the hippocampus of PC1/3 KO mice. Various behavioral tests reveal that in PC7 KO mice spatial memory is intact and plasticity of responding is mildly abnormal. Episodic and emotional memories are severely impaired, but both are rescued with the tyrosine receptor kinase B agonist 7,8-dihydroxyflavone. Altogether, these results support an in vivo role for PC7 in the regulation of certain ...

Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not

Sigma-Aldrich offers abstracts and full-text articles by [Erica D Smith, G Aleph Prieto, Liqi Tong, Ilse Sears-Kraxberger, Jeffrey D Rice, Oswald Steward, Carl W Cotman].

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are molecules which regulate the development and maintenance of specific functions in dif

Perhaps no other brain nutrient is receiving as much attention lately as DHA, especially after it was found to be a great way to increase BDNF. Scientists have been aggressively studying this critical brain fat for the past several decades for at least three reasons.. First, more than two-thirds of the dry weight of the human brain is fat, and one-quarter of that fat is DHA. From a structural point of view, DHA is an important building block for the membranes that surround healthy brain cells. These membranes include the areas where one brain cell connects to another, the synapses. This means that DHA is involved in the transmission of information from one neuron to the next and thus is fundamental for efficient brain function.. Second, DHA is one of natures important regulators of inflammation. Inflammation is responsible for a large number of brain maladies, including Alzheimers, Parkinsons, attention deficit hyperactivity disorder (ADHD), and multiple sclerosis. DHA naturally reduces the ...

Purpose : The concept that the brain-derived neurotrophic factor (BDNF) is a major trophic factor for retinal neurons is well-established. However, the cellular and molecular mechanisms governing BNDF production and its neuroprotective effect remain largely unknown. To determine the role of BDNF in neuroprotection in diabetic retinopathy (DR) and age-related macular degeneration (AMD), we investigated the mechanism of BDNF production/secretion by Müller cells (MCs) and of BDNF-mediated MC viability under diabetic and hypoxic conditions using both in vivo and in vitro models. Methods : BDNF production and expression were quantified with immunoblotting and ELISA analysis using a rat MC line (rMC1) and condtional gene knockout (KO) mice. MC viability was measured by live cell quantification. MG and neuronal density in mice was analyzed with immunohistochemistry and retinal morphology was examined with light microscopy. Results : In high glucose media, MC secreted a high level of BDNF which was ...

Abstract Background: Brain-derived neurotrophic factor (BDNF) could be as a molecular candidate for the development of bipolar disorder. We tried t..

Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were ...

Keywords: SKF 83959 brain-derived neurotrophic aspect tropomyosin receptor kinase B juvenile prefrontal cortex nucleus accumbens Launch Adolescence is an interval of maturation in the corticolimbic parts of the mind and proof shows that this stage of advancement may coincide with the original manifestation of symptoms connected with neuropsychiatric disease. Symptoms of despair and schizophrenia for instance show significant boosts during adolescence [1 2 a developmental period also connected with elevated awareness to psychostimulant-induced praise [3-6]. Brain-derived neurotrophic aspect (BDNF) an associate from the neurotrophin category of development factors MLN518 acts inside the central anxious program via the tropomyosin receptor kinase B (TrkB) to aid the success of existing neurons [7 8 maintain neuronal synapse integrity [9] and promote neuronal development and differentiation [8 10 Because of these important activities on neuronal plasticity BDNF continues to be postulated to become ...

JNeurosci Print ISSN: 0270-6474 Online ISSN: 1529-2401. The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturers claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.. ...

J Neuroinflammation. 2017 Aug 4;14(1):156. doi: 10.1186/s12974-017-0930-6.. Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis.. Xu D1, Lian D1, Wu J1, Liu Y2, Zhu M3, Sun J3, He D1, Li L4.. Author information. Abstract. BACKGROUND:. Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-derived neurotrophic factor (BDNF) has long been recommended for the treatment of CNS diseases due to its powerful neuro-survival properties, as well as its recently reported anti-inflammatory and anti-apoptotic effects in vitro and in vivo.. METHODS:. In this study, we investigated the effects of BDNF-related signaling on the inflammatory response and hippocampal apoptosis in ...

Brain-derived neurotrophic factor (BDNF) promotes the biochemical and morphological differentiation of selective populations of neurons during development. In this study we examined the energy requirements associated with the effects of BDNF on neuronal differentiation. Because glucose is the preferred energy substrate in the brain, the effect of BDNF on glucose utilization was investigated in developing cortical neurons via biochemical and imaging studies. Results revealed that BDNF increases glucose utilization and the expression of the neuronal glucose transporter GLUT3. Stimulation of glucose utilization by BDNF was shown to result from the activation of Na+/K+-ATPase via an increase in Na+ influx that is mediated, at least in part, by the stimulation of Na+-dependent amino acid transport. The increased Na+-dependent amino acid uptake by BDNF is followed by an enhancement of overall protein synthesis associated with the differentiation of cortical neurons. Together, these data demonstrate the

Antiepileptic drugs provide neuroprotection in several animal models of brain damage, including those induced by status epilepticus (SE). The mechanisms involved in this action are unknown, but neurotrophic factors such as brain-derived neurotrophic factor (BDNF) may play a role. In this study we investigated the changes in BDNF levels in rats in which SE had been induced by pilocarpine injection (400 mg/kg i.p.) and continued for several hours (unprotected group). In other animals (protected groups), SE was suppressed after 30 min by intraperitoneal injection of either diazepam (10 mg/kg) + pentobarbital (30 mg/kg) or paraldehyde (0.3 mg/kg). In diazepam + pentobarbital-treated rats the hippocampal damage caused by SE was significantly lower (p , 0.05) than in unprotected animals. In addition, 2 and 24 h after pilocarpine injection, the levels of BDNF mRNA were moderately increased in the unprotected group, but super-induced in protected animals, especially in the neocortex and hippocampus. A ...

The mind‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB) (BDNF‐TrkB) signalling pathway plays a crucial part in regulating learning and memory. offspring hippocampus cells using actual‐time PCR (RT‐PCR) and immunohistochemistry (IHC) respectively. The levels of phosphorylated‐TrkB (phospho‐TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure NSC-207895 to propofol on day time E18 impaired spatial learning and memory space of rat offspring decreased mRNA and protein levels of BDNF and TrkB and decreased the levels of both phospho‐TrkB and synaptophysin in the hippocampus. Furthermore the TrkB agonist 7 8 (7 8 reversed all the observed changes. Treatment with 7 8 experienced no significant effects within the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory space of offspring by disturbing the ...

Up-regulation of nestin expression was significantly induced in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice in our previous observation [Brain Res 925 (2002) 9]. We hypothesized that the nestin-expressing cells might play an important role in the pathogenesis of parkinsonian model, and characterization of these nestin-expressing cells was studied by RT-PCR, immunohistochemistry and semi-quantitative analysis for various markers of glial fibrillary acid protein (GFAP), S-100, neuronal nuclear specific protein (NeuN), β-tubulin, Ki-67 and brain-derived neurotrophic factor (BDNF) expression in MPTP-treated C57/BL mice. Firstly, significant increasing in both nestin protein and mRNA was found in MPTP-treated mice. Up-regulation of nestin expression started at day 1, peaked at day 3, and gradually went down at days 7-21 in the neostriatum after MPTP treatment. Secondly, double immunofluorescence indicated that almost all of nestin-positive cells exhibited ...

Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17 β -estradiol (E2) on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX) rats. The animals were divided into six groups: (i) nonstressed sham-operated control, (ii) stressed sham-operated control, (iii) nonstressed OVX, (iv) stressed OVX, (v) stressed OVX treated with E2 (20 μ g daily, sc), and (vi) stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally). Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH) and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration ...

Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17 β -estradiol (E2) on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX) rats. The animals were divided into six groups: (i) nonstressed sham-operated control, (ii) stressed sham-operated control, (iii) nonstressed OVX, (iv) stressed OVX, (v) stressed OVX treated with E2 (20 μ g daily, sc), and (vi) stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally). Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH) and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration ...

Alveolar epithelial regeneration is essential for recovery from devastating lung diseases. This process occurs when type II alveolar pneumocytes (AT2 cells) proliferate and transdifferentiate into type I alveolar pneumocytes (AT1 cells). We used genome-wide analysis of chromatin accessibility and gene expression following acute lung injury to elucidate repair mechanisms. AT2 chromatin accessibility changed substantially following injury to reveal STAT3 binding motifs adjacent to genes that regulate essential regenerative pathways. Single-cell transcriptome analysis identified brain-derived neurotrophic factor (Bdnf) as a STAT3 target gene with newly accessible chromatin in a unique population of regenerating AT2 cells. Furthermore, the BDNF receptor tropomyosin receptor kinase B (TrkB) was enriched on mesenchymal alveolar niche cells (MANCs). Loss or blockade of AT2-specific Stat3, Bdnf or mesenchyme-specific TrkB compromised repair and reduced Fgf7 expression by niche cells. A TrkB agonist improved

We investigated whether δ-opioid receptor (DOR)-induced neuroprotection involves the brain-derived neurotrophic factor (BDNF) pathway. We studied the effect of DOR activation on the expression of BDNF and other proteins in the cortex of C57BL/6 mice exposed to hypoxia (10% of oxygen) for 1-10 days. The results showed that: (1) 1-day hypoxia had no appreciable effect on BDNF expression, while 3- and 10-day hypoxia progressively decreased BDNF expression, resulting in 37.3% reduction (p < 0.05) after 10-day exposure; (2) DOR activation with UFP-512 (1 mg/kg, i.p., daily) partially reversed the hypoxia-induced reduction of BDNF expression in the 3- or 10-day exposed cortex; (3) DOR activation partially reversed the hypoxia-induced reduction in functional TrkB (140-kDa) and attenuated hypoxia-induced increase in truncated TrkB (90-kDa) in the 3- or 10-day hypoxic cortex; and (4) prolonged hypoxia (10 days) significantly increased TNF-α level and decreased CD11b expression in the cortex, which was

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system. Neuronal injury and oxidative stress in AD increases the level of inflammatory cytokines. Curcumin has antioxidant and neuroprotective properties. The aim of this study was to determine the effect of curcumin on hippocampal levels of brain-derived neurotrophic ...

Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of

Brain-derived neurotrophic factor (BDNF) has long been known as a trophic factor involved in survival, differentiation, and maintenance of neuronal populations in the central nervous system. In addition to these effects, BDNF has emerged as a major activity-dependent regulator of synaptic transmission and plasticity in many brain areas, most notably the neocortex and hippocampus. Pre- and postsynaptic localization of BDNF and its cognate receptor, tropomyosin receptor kinase B (TrkB) at glutamate synapses in particular, make it an ideal candidate for rapidly fine-tuning excitatory transmission and modulating the ability of synapses to undergo activity-dependent plasticity. Furthermore, N-methyl-D-asparate (NMDA) receptors, which play an important role in some forms of plasticity, are a primary target of BDNF-TrkB receptor signaling. Although BDNF appears to have pre- and postsynaptic effects on glutamatergic transmission, consistent with localization of TrkB receptors to axon terminals and dendritic

Background: Antidepressant drugs (ADs) have been shown to activate BDNF (brain-derived neurotrophic factor) receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. Methodology: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. Principal Findings: Using a chemical-genetic TrkB(F616A) mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase ...

Could an alternative version of your brain-derived neurotropic factor be an excuse for your failed road test?. According to research published in the Journal, Cerebral Cortex, by Stephanie McHughen et.al., a key SNP in BDNF (valine 66 mutated to methionine) impacts learning and memory functions, cognitive tools which happen to be crucial for operating an automobile.. During one of the described experiments, subjects were seated at a computer, with attached steering wheel as they had to keep the virtual car on a black line in the center of the screen. Subjects got to learn the driving circuit by following the car on 15, 60 second trials. While both groups of subjects (those who had the normal valine allele, and those with the val66met SNP) started at similar levels of ability, and showed short term learning. During the trials however, val66met subjects showed less learning, and made more mistakes while learning. By day 5 of training, those with the val66met allele showed less ability to retain ...

Human brain derived neurotrophic element (BDNF) acting through the tropomyosin-related kinase receptor B (TrkB) enhances neuromuscular transmission in the diaphragm muscle mass of adult mice, reflecting presynaptic effects. vehicle treatment. In early old age (18 months), presynaptic terminal volume decreased compared to 6 month older diaphragm NMJs (~20 %). Inhibition of TrkB kinase activity significantly decreased the presynaptic terminal volume (~20 %) and engine end-plate 2D planar area (~10 %), self-employed of age group. Inhibition of TrkB kinase activity in early old age significantly reduced overlap of pre- and post-synaptic constructions and improved the proportion of denervated NMJs (to ~20 %). Collectively these results support a period of susceptibility in early old age when BDNF/TrkB signaling at diaphragm NMJs helps the maintenance of NMJs structure and muscle mass innervation. software of 1118460-77-7 IC50 BDNF enhanced neuromuscular transmission in 18 month older mice, similar to ...

Neurotrophic factors have an established developmental role in regulating the survival and specification of sensory neurons. However, these factors continue to exert an important influence on sensory neurons throughout the postnatal period and into adult life. In adulthood, approximately one-half of nociceptors are dependent on nerve growth factor (NGF) for trophic support, whereas the other half are sensitive to glial cell line-derived neurotrophic factor (GDNF). It is now known that many chronic pain states are maintained by widespread changes in the anatomy, neurochemistry, and function of the sensory nervous system both at the level of the primary sensory neuron and the dorsal horn of the spinal cord. Trophic factors appear to orchestrate many of these dynamic changes. This review highlights some of the key roles played by these molecules and in particular the role of NGF in the peripheral sensitization of nociceptors and brain-derived neurotrophic factor (BDNF) as a central pain modulator.

Endocytosis of Trk (tropomyosin-related kinase) receptors is critical for neurotrophin signal transduction and biological functions. However, the mechanism governing endocytosis of TrkB (tropomyosin-related kinase B) and the specific contributions of TrkB endocytosis to downstream signaling are unknown. In this study, we report that blocking clathrin, dynamin, or AP2 in cultured neurons of the central nervous system inhibited brain-derived neurotrophic factor (BDNF)-induced activation of Akt but not ERK. Treating neurons with the clathrin inhibitor monodansylcadaverine or a peptide that blocks dynamin function specifically abrogated Akt pathway activation in response to BDNF but did not affect the response of other downstream effectors or the up-regulation of immediate early genes neuropeptide Y and activity-regulated cytoskeleton-associated protein. Similar effects were found in neurons expressing small interfering RNA to silence AP2 or a dominant negative form of dynamin that inhibits ...

Neurotrophic factors (NTFs) are a family of biomolecules - nearly all of which are peptides or small proteins - that support the growth, survival, and differentiation of both developing and mature neurons.[1][2][3] Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases,[2] usually a receptor tyrosine kinase. In the mature nervous system, they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories.[2] Neurotrophic factors also promote the initial growth and development of neurons in the central nervous system and peripheral nervous system, and they are capable of regrowing damaged neurons in test tubes and animal models.[1][4] Some neurotrophic factors are also released by the target tissue in order to guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family ligands (GFLs), and (3) neuropoietic ...

Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary &alpha;

Purpose: : During NMDA-induced cell death in the neural retina, there is an elevation of the nuclear isoform of CaMKIIα (CaMKIIαB). This result leads to the question of how CaMKIIαB might be involved in either a cell death or cell survival pathway, for example, in retinal ganglion cells (RGCs). The purpose of this study is to investigate if CaMKIIα regulates BDNF expression in RGCs. Methods: : Highly purified RGCs or dissociated retinal cells were obtained from P6-8 SD rat eyes and treated with glutamate (200-1000uM) for the indicated times. Glutamate cytotoxicity on RGCs and localization of CaMKIIα was determined by cell counting and immunostaining, respectively. To identify the role of CaMKIIα in regulating BDNF expression, CaMKIIαB expression vector was constructed and over-expressed in cells of the RGC-5 cell line, and cell viability was assayed. Specific siRNAs to knock down CaMKIIαB or CaMKIIα were then tested in CaMKIIαB-transfected or non-transfected RGC-5 cells. The siRNAs ...

Ionotropic glutamate receptors mediate most excitatory synaptic transmission in mammalian brain, and play important roles in neuronal development and synaptic plasticity. In particular, long-term potentiation (LTP) and long-term depression (LTD) are generally considered to represent cellular mechanisms involved in certain forms of learning and memory. Calpain is a calcium-dependent neutral protease that plays significant roles in synaptic plasticity, cell motility, as well as in various forms of neurodegeneration. We compared the rates of calpain-mediated truncation of GluR1 and GluR2 subunits with those of GluR1 phosphorylated at serine 831 or serine 845, and GluR2 phosphorylated at serine 880. Rat brain membranes were treated with calpain and calcium and levels of total and phosphorylated GluR1 and GluR2 subunits were analyzed by western blots. Rates of calpain-mediated truncation of phosphorylated GluR1 (either at serine 831 or 845) were much slower than for total GluR1. On the other hand, ...

Genetic and pharmacological perturbations suggest that tyrosine receptor kinase B (trkB) receptor activation promotes limbic epileptogenesis, but whether or where trkB activation occurs during epileptogenesis is uncertain. Because activation of trk receptors involves phosphorylation of specific tyrosine residues (Segal et al., 1996), the availability of antibodies that selectively recognize the phosphorylated form of trk receptors at the Shc site permits an immunohistochemical assessment of trk receptor activation. We reported previously increased phospho-specific trk (p-trk) immunoreactivity in the mossy fiber pathway of the hippocampus during epileptogenesis in rats (Binder et al., 1999b). Because the p-trk antibody does not distinguish among trkA, trkB, and trkC, the identity of the neurotrophin receptor(s) undergoing phosphorylation was uncertain. The development of mice carrying a point mutation of the Shc binding site (Y515F) in the trkB gene (trkB(shc)) provided an opportunity to test the

Nicotine exposure enhances Pavlovian conditioned approach (PCA), or the learned approach to reward-predictive cues. While females show elevated approach to conditioned stimuli compared to males, potentially indicating heightened addiction vulnerability, it is unknown how sex may interact with nicotine to influence approach behavior. Additionally, brain-derived neurotrophic factor (BDNF) levels can be altered significantly after repeated nicotine exposure, suggesting a potential mechanism contributing to nicotine-induced behavioral phenotypes. The present study investigated the role of sex on nicotine-induced changes to stimulus-response behavior and associated BDNF protein levels. Male and female rats were exposed to nicotine (0.4 mg/kg, subcutaneously) or saline 15 min prior to each PCA session. PCA training consisted of 29 sessions of 15 trials, in which a 30-s cue presentation ended concurrently with a sucrose reward (20% w/v in water, 100 μL), and a 120-s variable intertrial interval occurred

Neurotrophin signaling impacts development and health of oligodendrocyte lineage cells. Brain-derived neurotrophic factor (BDNF) has been of particular interest. BDNF increases DNA synthesis in cultured basal forebrain oligodendrocyte progenitors (Vant Veer et al., 2009) and enhances oligodendrocyte differentiation to myelin protein-expressing cells (Du et al., 2006). Moreover, BDNF deficient mice exhibit deficits in progenitors and myelin protein expression (Vondran et al., 2010) and the conditional knock-out of the BDNF receptor TrkB from mature, MBP+ oligodendrocytes results in reduced myelin thickness in both the spinal cord and the corpus callosum (Wong et al., 2013).. These effects may be relevant to in vivo demyelination. For example, in the cuprizone demyelination model expression of BDNF is decreased in the corpus callosum, and animals deficient in BDNF exhibit a more severe loss of myelin protein in the lesioned corpus callosum than do their wild-type littermates (VonDran et al., ...

Fig. 7. Protein expression levels of BDNF, TrkB, p-CREB and p-ERK in the brain of rats after different treatments. 24 female Sprague-Dawley rats with ovariectomy underwent intraperitoneal administration of estrogen or its vehicle. 12 rats of sham-operated group only underwent the resection of a bit of fat around bilateral ovaries. All these rats were injected with 10 mg/kg NTG once a week and the injection was repeated five times. The rats were sacrificed during the migraine attacks (4 h after the fifth injection) or the headache-free intervals (24 h after the fifth injection). After rats were anaesthetized with ketamine and xylazine (i.p.), the whole brain was removed and subjected to RT-PCR assay. *P,0.05, **P,0.01 between each group (n=12, ANOVA followed by a Tukeys post hoc test for multiple comparisons). BDNF, brain-derived neurotrophic factor; TrkB, tropomyosin receptor kinases; p-ERK, phosphorylated extracellular signal-regulated kinase; p-CREB, phosphorylated c-AMP-responsive element ...

Sigma-Aldrich offers abstracts and full-text articles by [Lisa M McFadden, Paula L Vieira-Brock, Glen R Hanson, Annette E Fleckenstein].

TY - JOUR. T1 - Small molecules activating TrkB receptor for treating a variety of CNS disorders. AU - Zeng, Yan. AU - Wang, Xiaonan. AU - Wang, Qiang. AU - Liu, Shumin. AU - Hu, Xiamin. AU - Mcclintock, Shawn M.. PY - 2013/11/1. Y1 - 2013/11/1. N2 - The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNFs neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of ...

Infusing brain-derived neurotrophic factor (BDNF) into the infralimbic (IL) prefrontal cortex is capable of inducing extinction. Little is known, however, about the circuits mediating BDNF effects on extinction or the extent to which extinction requires BDNF in IL. Using local pharmacological infusion of BDNF protein, or an antibody against BDNF, we found that BDNF in the IL, but not prelimbic (PL) prefrontal cortex, is both necessary and sufficient for fear extinction. Furthermore, we report that BDNF in IL can induce extinction of older fear memories (14 days) as well as recent fear memories (1 day). Using immunocytochemistry, we show that BDNF is increased in the ventral hippocampus (vHPC), but not IL or PL, following extinction training. Finally, we observed that infusing BDNF into the vHPC increased the firing rate of IL, but not PL neurons in fear conditioned rats. These findings indicate that an extinction-induced increase in BDNF within the vHPC enhances excitability in IL targets, ...

Author: Mueller, Karsten et al.; Genre: Journal Article; Published in Print: 2016-02; Keywords: Brain-derived neurotrophic factor (BDNF); Brain connectivity; Motor cortex; Eigenvector centrality (EC); Functional magnetic resonance imaging (fMRI); Resting-state fMRI; Title: Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain: A resting-state fMRI pilot study

From a treatment standpoint, methods of increasing neuroplasticity can include physical exercise, which has been found to increase neurotrophic factors, a kind of fertilizer for the brain, in addition to stimulating angiogenesis. Cognitive exercise can also increase a specific type of fertilizer called brain-derived neurotrophic factor (BDNF) and increases synaptogenesis. The question then arises, What if these therapy activities were combined? For example, what if you had someone walking on a treadmill while performing some type of cognitive activity so that you stimulate neurotrophic factors on two fronts? One study actually did find that such a combination of activities can exponentially enhance the production of neurotrophic factors. ...

TY - JOUR. T1 - Glucocorticoid regulates TrkB protein levels via c-Cbl dependent ubiquitination. T2 - A decrease in c-Cbl mRNA in the prefrontal cortex of suicide subjects. AU - Pandya, Chirayu. AU - Kutiyanawalla, Ammar. AU - Turecki, Gustavo. AU - Pillai, Anilkumar. PY - 2014/7. Y1 - 2014/7. N2 - Brain derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays a crucial role in neurodevelopment and plasticity. Stress and glucocorticoids have been shown to alter TrkB signaling in neurons, and defects in TrkB expression have been reported in the prefrontal cortex of suicide subjects. Glucocorticoid treatment has been shown to induce deleterious effects on the neuronal maturation. However, the mechanisms involved in the regulation of TrkB by glucocorticoid during neurodevelopment are not clear. Here we show that acute corticosterone exposure induced posttranslational upregulation of TrkB in primary cortical neurons (days in vitro 4, DIV4), which was blocked by the proteasome ...

Background: Huntingtons disease (HD) is a genetically inherited, fatal neuropsychiatric disorder which strikes 1/10,000 people. The cause is a repeat expansion in the Huntingtin gene which leads to progressive brain degeneration, ultimately resulting in death after 15-20 years. HD passes from generation to generation. Each child of a parent with HD has a 50% chance of inheriting the HD mutation. There is currently no treatment, therapy or medication that will delay the onset of the disease or slow its progression. All currently available treatments are palliative, which focus on symptom management alone. There is currently no cure for HD. Proposed therapy: We propose a novel therapy for HD: implantation of mesenchymal stem cells engineered to secrete Brain-Derived Neurotrophic Factor (MSC/BDNF). BDNF levels are reduced in the brains of HD patients. BDNF has been shown in numerous transgenic HD mouse studies to prevent cell death and to stimulate the growth and migration of new neurons in the ...

Introduction To investigate the neuroprotective effect and mechanism of DL-3-n-butylphthalide (NBP) on the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) and its downstream signalling pathway after cerebral ischemia/reperfusion injury (CIRI) in rats. Material and methods...

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association

Research Summary. Research in my laboratory is centered around signalling events, particularly those that involve intracellular Ca2+ and the major Ca2+ -binding regulatory protein calmodulin. Two systems we are investigating are the regulation of protein synthesis and the control of endocytosis by Ca2+, both of which involve (different) calmodulin-regulated events. We are also interested in the mechanism of action of neurotrophic factors like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) as they relate to the effects of these proteins on CNS neurons. Part of the action of these factors also involves Ca2+. Current projects. Neurotrophic factors and CNS neurons We have shown that primary cultures of rat embryonic hippocampal neurons can be used for biochemical investigations of the signal transduction pathways activated by BDNF and neurotrophin-3. These cells homogeneously express the receptors for these neurotrophins (receptor tyrosine kinases called TrkB and TrkC), and ...

TY - JOUR. T1 - BDNF plasma levels variations in major depressed patients receiving duloxetine. AU - Fornaro, Michele. AU - Escelsior, Andrea. AU - Rocchi, Giulio. AU - Conio, Benedetta. AU - Magioncalda, Paola. AU - Marozzi, Valentina. AU - Presta, Andrea. AU - Sterlini, Bruno. AU - Contini, Paola. AU - Amore, Mario. AU - Fornaro, Pantaleo. AU - Martino, Matteo. PY - 2015/5/1. Y1 - 2015/5/1. N2 - It has been frequently reported that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of major depressive disorder (MDD). Objective of the study was to investigate BDNF levels variations in MDD patients during antidepressant treatment with duloxetine. 30 MDD patients and 32 healthy controls were assessed using Hamilton Depression Scale (HAM-D) and monitored for BDNF plasma levels at baseline, week 6 and week 12 of duloxetine treatment (60 mg/day) and at baseline, respectively. According to early clinical response to duloxetine (defined at week 6 by reduction ,50 % ...

The development of cerebellar cortex is strongly impaired by thyroid hormone (T3) deficiency, leading to altered migration, differentiation, synaptogenesis, and survival of neurons. To determine whether alteration in the expression of neurotrophins and/or their receptors may contribute to these impairments, we first analyzed their expression using a sensitive RNAse protection assay and in situ hybridization; second, we administered the deficient neurotrophins to hypothyroid animals. We found that early hypothyroidism disrupted the developmental pattern of expression of the four neurotrophins, leading to relatively higher levels of NGF and neurotrophin 4/5 mRNAs and to a severe deficit in NT-3 and brain-derived neurotrophic factor (BDNF) mRNA expression, without alteration in the levels of the full-length tyrosine kinase (trk) B and trkC receptor mRNAs. Grafting of P3 hypothyroid rats with cell lines expressing high levels of neurotrophin 3 (NT-3) or BDNF prevented hypothyroidism-induced cell ...

Wong, J. & Garner, B. (2012). Evidence that truncated TrkB isoform, TrkB-Shc can regulate phosphorylated TrkB protein levels. Biochemical and Biophysical Research Communications, 420 (2), 331-335 ...

Given that both clinical and preclinical studies suggest that BDNF may be involved in the therapeutic action of antidepressants, BDNF appears to be a good candidate gene for the pharmacogenetic study of antidepressants. In our 2003 study on 110 MDD outpatients, we examined the association between the BDNF Val66Met polymorphism and response to 4-week antidepressant (fluoxetine) treatment.17 A trend (p=0.086) to higher total HAM-D-score percentage change was noted for the Val/Met-heterozygote patients in comparison to those bearing the homozygote (Val/Val or Met/Met). While similar findings have been reported in some of the subsequent studies of this polymorphism and the antidepressant response23,24, other studies demonstrated a better response in subjects with the Met variant25-27 or they found no association at all (Table 1).28,29 The inconsistencies in these findings might be due to the small sample sizes used in some of the studies. They could also have arisen as the result of differences in ...

phdthesis{e6a24cb9-3a1a-4b11-91f1-3152114bb8fb, abstract = {Enriched environment (EE) housing significantly ameliorates neurological deficits induced by cortical brain ischemia without changing infarction size, suggesting that EE-related functional benefits are associated with neuronal plasticity events in the remaining tissue. Brain-derived neurotrophic factor (BDNF), nerve growth factor-induced gene A (NGFI-A) and corticosteroid receptors (mineralocorticoid receptor, MR; glucocorticoid receptor, GR) have been demonstrated to be involved in brain plasticity. The purpose of this thesis was to determine if post-ischemic housing conditions had a significant effect on transcription and/or translation of BDNF, NGFI-A and corticosteroid receptors. We found that BDNF gene was down regulated in EE-housed rats when compared to the rats housed in standard cages at 2~12 days after cortical brain ischemia in peri-infarct cortex, contralateral cortex and bilateral hippocampus. The protein level of BDNF in ...

Objective To investigate the association between chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in rats and expressions of brain-derived neurotrophic factor (BDNF) and S100ß in the hippocampal and prefrontal cortex. Methods Rats were randomly assigned to three groups:saline control group,saline+CUMS group,and citalopram +CUMS group. CUMS was used for depression modeling in rats. Depressive-like behavior in rats were evaluated by open-field test,sucrose preference test,and novel object recognition test. S100ß and BDNF expressions were tested by enzyme-linked immunosorbent assay. Results Rats in the saline+CUMS group had significantly lower score in sucrose preference [(52.48±13.14)%],basic motor tasks [(845.8±371.4)s],fine motor tasks [(565.6±211.9)s],and longer resting time [(282.6±11.8)s] compared to the control group [(84.30±6.15)% (t=7.49,P=0.000),(1239.1±281.6)s (t=2.83,P=0.008),(801.8±150.9)s (t=3.05,P=0.003),(268.2±12.8)s (t=2.72,P=0.001)]. Compared ...

Full Text - Retinal ischemia emerges in many ocular diseases and is a leading cause of neuronal death and dysfunction, resulting in irreversible visual impairment. We previously reported that brain-derived neurotrophic factor (BDNF)-expressing human 293T cells could steadily express BDNF and play a protective role in ARPE-19 cells, a human retinal epithelial cell line. Thus, we hypothesized that exosomes might be essential in the interaction between BDNF-expressing 293T cells and recipient cells. The study investigated whether exosomes derived from BDNF-expressing 293T cells (293T-Exo) can be internalized by ischemic retinal cells and exert neuroprotective roles. The results demonstrated that 293T-Exo significantly attenuated the loss of cell proliferation and cell death in R28 cells in response to oxygen-glucose deprivation treatment. Mechanistic studies revealed that the endocytosis of 293T-Exo by R28 cells displayed dose- and temperature-dependent patterns and may be mediated by the caveolar

Title:Hippocampal Neurogenesis, Neurotrophic Factors and Depression: Possible Therapeutic Targets?. VOLUME: 13 ISSUE: 10. Author(s):Gianluca Serafini, Shawn Hayley, Maurizio Pompili, Yogesh Dwivedi, Goutam Brahmachari, Paolo Girardi and Mario Amore. Affiliation:Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, IRCCS San Martino, Largo Rosanna Benzi 10, 16100, Genoa, Italy.. Keywords:Antidepressant drugs, hippocampal neurogenesis, major depression, neurotrophic factors, therapeutic targets.. Abstract:Major depression is one of the leading causes of disability and psychosocial impairment worldwide. Although many advances have been made in the neurobiology of this complex disorder, the pathophysiological mechanisms are still unclear. Among the proposed theories, impaired neuroplasticity and hippocampal neurogenesis have received considerable attention. The possible association between hippocampal ...

Although previous studies of Huntingtons disease (HD) have addressed many potential mechanisms of striatal neuron dysfunction and death, it is also known based on clinical findings that cortical function is dramatically disrupted in HD. With respect to disease etiology, however, the specific molecular and neuronal circuit bases for the cortical effects of mutant huntingtin (htt) have remained largely unknown. In the present work we studied the relation between the molecular effects of mutant htt fragments in cortical cells and the corresponding behavior of cortical neuron microcircuits using a novel cellular model of HD. We observed that a transcript-selective diminution in activity-dependent BDNF expression preceded the onset of a synaptic connectivity deficit in ex vivo cortical networks, which manifested as decreased spontaneous collective burst-firing behavior measured by multi-electrode array substrates. Decreased BDNF expression was determined to be a significant contributor to ...

Additionally, experience of an enriched environment brings about cellular changes in neurons, including synapse creation in the hippocampus, which is responsible for memory, and an increase in neurotrophins essential for neural function such as brain-derived neurotrophic factor (BDNF). However, the mechanism of these cellular and behavioral changes remained unknown.. Professor Nobutaka Hirokawa and his colleagues at the University of Tokyos Graduate School of Medicine have shown for the first time that the motor protein KIF1A, known to be involved in the transport of compounds essential for neural signaling, has a vital role in memory and learning enhancement due to an enriched environment.. The research group determined that the quantity of BDNF and KIF1A was elevated in the hippocampi of mice raised in an enriched environment. However, even when raised in an enriched environment, a genetically-engineered mouse with a reduced ability to express KIF1A showed no increase in hippocampal synapse ...