NeurogenesisGliosisEpilepsyMicroRNAsHippocampusSynapticConvulsiveEpileptic seizuresHyperexcitabilityNeuronsAbnormalitiesAntiepileptic drugsStatus epilepticusSpontaneousDifferentiationDysfunctionAberrantIntracellularGeneCardiacTargetsBiomarkerNeuroinflammationCellsExpressionOnsetCognitiveMitochondrialAntisenseSpecificallyGeneticDeathLevelsMiceFunctionProteinActivityCellEffects
Neurogenesis4
- Gene expression programmes drive many of the changes underlying network reorganisation in epileptogenesis, including neurodegeneration, astrogliosis, microgliosis, aberrant neurogenesis and restructured local and distant neuronal contacts, among other changes [ 3-5 ]. (researchsquare.com)
- Convulsive seizures promote adult hippocampal neurogenesis (AHN) through a transient activation of neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). (ehu.eus)
- Experimental reduction of Foxp2 in the cortex of embryonic mice through either shRNA or overexpression of the dominant negative KE form of FoxP2 repressed the transition from radial precursor to immediate neuronal progenitor, resulting in decreased cortical neurogenesis (Tsui, Vessey, Tomita, Kaplan, & Miller, 2013). (comparative-cognition-and-behavior-reviews.org)
- Secretagogins are EF HAND MOTIF-containing calcium-binding proteins that are involved in early neuronal migration and neurogenesis. (lookformedical.com)
Gliosis4
- Sequencing as well as functional studies using antisense oligonucleotides, indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. (researchsquare.com)
- Indeed, functional studies in animals, mainly using antisense oligonucleotides (ASOs) termed antagomirs, have demonstrated that targeting miRNAs can alter evoked and spontaneous seizures and neuropathological outcomes including neuronal loss and gliosis [ 11 ]. (researchsquare.com)
- The changes observed all point to causes that underlie pathogenesis of epilepsy, such as neuronal death, gliosis, neuroinflammation and changes to ion channel and neurotransmitter receptors, neural plasticity, and remodeling [8]. (evolutamente.it)
- The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal death, gliosis and chronic seizures. (uni-frankfurt.de)
Epilepsy12
- miR-324-5p downregulates KV4.2, exacerbating conditions that lead to seizure onset, and downregulation of miR-324-5p in mouse models of epilepsy is seizure-suppressive. (wikipedia.org)
- Continuous EEG monitoring after status epilepticus revealed an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. (researchsquare.com)
- Prolonged or repeated seizures are damaging to the brain and can establish lasting states of hyperexcitability that produce recurrent spontaneous seizures (epilepsy) [ 1 , 2 ]. (researchsquare.com)
- Expression of various miRNAs is dysregulated in experimental models of status epilepticus and in resected brain tissue from patients with drug-resistant temporal lobe epilepsy [ 11-13 ]. (researchsquare.com)
- Though current antiseizure medications (ASMs) can control seizures in two thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one third, as does the lack of disease-modifying therapies. (medscape.com)
- Epilepsy occurs throughout the age-span and is often characterized by spontaneous non-provoked seizures. (evolutamente.it)
- Unfortunately, at least one-third of affected individuals continue to experience spontaneous recurrent seizures as the entire arsenal of anti-seizure drugs (ASD) is ineffective in the prevention of development and progression of epilepsy in those patients [1]. (evolutamente.it)
- Recent epilepsy research and development has departed from traditional anti-seizure drugs to focus on epigenetics in the prevention of epilepsy and its progression. (evolutamente.it)
- Anti-seizure drug treatment are ineffective in the prevention of seizures in one third of patients who suffer from epilepsy is probably due to the fact that treatment by drugs is basically a pharmacological 'top-down' approach, whereas evolution began from the opposite direction. (evolutamente.it)
- Serotonin 5-HT2 receptor agonists have shown efficacy in treating seizure disorders, such as epilepsy. (bioworld.com)
- Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy characterized by recurrent seizures originating in the hippocampus and with sprouting of mossy fiber axons that contribute to new recurrent synaptic excitability in the dentate gyrus (DG). (bioworld.com)
- Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. (uni-frankfurt.de)
MicroRNAs3
- The miRNA quickly gained traction in scientific literature, appearing in articles about the evolutionary conservation of microRNAs, HIV, cancer, and other topics within a few years. (wikipedia.org)
- Small noncoding RNAs called microRNAs (miRNA) negatively regulate gene expression by sequence-specific targeting of protein-coding transcripts [ 6 ]. (researchsquare.com)
- In the case of RNA molecules that bind target RNA segments, such as microRNAs (miRNAs), the altered base pairing can change binding specificities. (biomedcentral.com)
Hippocampus1
- miR-22-3p (hereafter miR-22), a conserved miRNA that is expressed throughout the body, including the brain [ 14 , 15 ], was previously identified among upregulated miRNAs within the mouse hippocampus contralateral to the epileptogenic zone in the intraamygdala kainic acid model of status epilepticus [ 16 ]. (researchsquare.com)
Synaptic3
- Gene targets of the altered miRNAs in all the ASD subgroups were enriched in pathways of neuronal development and synaptic plasticity, along with cell proliferation/differentiation. (frontiersin.org)
- is credited with describing the CNS isoform of the MECP2 gene which is responsible for neuronal and synaptic function throughout the brain. (tayshagtx.com)
- Finally, in addition to confirming disrupted pathways and identifying novel hits in neuronal structure and synaptic transmission, our data indicate aberrant myelination, inflammation, and vascular disruption. (biomedcentral.com)
Convulsive2
- The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population," the company said in a news release . (medscape.com)
- The zinc compound reduces the degree of convulsive activity, neuronal death and the intensity of apoptosis. (ihna.ru)
Epileptic seizures1
- Currently third generation antiepileptic drugs are designed to suppress neuronal hyperexcitability and thereby, able to suppress epileptic seizures. (evolutamente.it)
Hyperexcitability2
- Neuronal hyperexcitability in Alzheimer's disease: what are the drivers behind this aberrant phenotype? (nature.com)
- Importantly, activity recordings at the level of single neurons, neuronal networks or even entire brain regions consistently show hyperexcitability in the early stages of AD (summarized in Table 1 ). (nature.com)
Neurons5
- in early 2004 that identified 32 entirely new miRNAs from cultured rat cortical neurons using miRNA cloning and RNA analysis. (wikipedia.org)
- It is found in well-defined populations of NEURONS and is involved in CALCIUM SIGNALING and NEURONAL PLASTICITY. (lookformedical.com)
- A calbindin protein that is differentially expressed in distinct populations of NEURONS throughout the vertebrate and invertebrate NERVOUS SYSTEM, and modulates intrinsic neuronal excitability and influences LONG-TERM POTENTIATION. (lookformedical.com)
- Neuron] Using patient-derived dopaminergic neurons, investigators found that phosphorylation of parkin by Ca 2+ /calmodulin-dependent protein kinase 2 at Ser9 led to activation of parkin in a neuronal-activity-dependent manner. (stemcellsciencenews.com)
- Nature Communications] Scientists systematically identified over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. (stemcellsciencenews.com)
Abnormalities2
- This study explored whether serum miRNAs are associated with both altered innate immune responses and changes in mitochondrial respiration as a link of regulatory mechanisms for these two common abnormalities in ASD subjects. (frontiersin.org)
- Our preliminary findings indicate that neuronal abnormalities in the striatum of an ASD mouse model showing autistic-like behaviors are accompanied by microglia-associated neuroinflammation and reduction of the pro-resolution activity. (autism.org)
Antiepileptic drugs1
- Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. (biomedcentral.com)
Status epilepticus1
- Advances within the past decade has shown that genome-wide DNA methylation changes occur in prolonged seizures (status epilepticus), as well as epileptic tolerance, which is an endogenous response system activated in the brain by a seizure episode. (evolutamente.it)
Spontaneous4
- Inhibiting miR-22 using intracerebroventricular injection of an ASO increased the frequency of spontaneous seizures, indicating a protective role in the model [ 16 ]. (researchsquare.com)
- DNA methylation was first associated in the pathogenesis of seizures in the mid 2000's where in vitro studies demonstrated a decrease of spontaneous excitatory neurotransmission and network activity when enzymes responsible for DNA methylation, DNA methyltransferases, were inhibited pharmacologically [2]. (evolutamente.it)
- Remarkably, the majority of these circRNAs were changed at the time of the occurrence of the first spontaneous seizure (DOFS). (uni-frankfurt.de)
- It reveals an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. (uni-frankfurt.de)
Differentiation1
- miRNAs are essential for brain development and function, with multiple miRNAs enriched in specific cell types where they regulate differentiation, structure and neurophysiological properties [ 9 , 10 ]. (researchsquare.com)
Dysfunction3
- Angelman Syndrome is a uncommon neurodevelopmental dysfunction characterised by impaired communication expertise, ataxia, motor and steadiness deficits, mental disabilities, and seizures. (chxa.com)
- Editorial: Glial heterogeneity: impact on neuronal function and dysfunction. (unil.ch)
- The results of this study will provide crucial information on the role of alterations in the pro-inflammatory and pro-resolution pathways in ASD pathophysiology, and on the capability of the multimodal stimulation provided by environmental enrichment to revert such alterations and the ensuing neuronal and behavioral dysfunction. (autism.org)
Aberrant1
- Specifically, we discuss contributors to aberrant neuronal excitability, including abnormal levels of intracellular Ca 2+ and glutamate, pathological amyloid β (Aβ) and tau, genetic risk factors, including APOE , and impaired inhibitory interneuron and glial function. (nature.com)
Intracellular1
- Additionally, miR-324-5p is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. (wikipedia.org)
Gene3
- Individual miRNAs are capable of regulating gene networks by interacting with multiple targets or by suppressing transcriptional controllers [ 6 , 8 ]. (researchsquare.com)
- Gene targets of the altered miRNAs in the high and/or low IL-1β/IL-10 ratio ASD subgroups were enriched in pathways critical for monocyte functions and metabolic regulation. (frontiersin.org)
- TSHA-102 is designed to deliver a healthy version of the MECP2 gene as well as the miRNA-Responsive Auto-Regulatory Element, miRARE, platform technology to control the level of MECP2 expression. (tayshagtx.com)
Cardiac2
- You can record from neuronal or cardiac cultures, stem cells, or brain or cardiac slices. (multichannelsystems.com)
- Individuals with Rett syndrome also show symptoms that include loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments, breathing issues and sleep disturbances. (tayshagtx.com)
Targets1
- Interestingly, both strands of miR-324's pre-miRNA hairpin loop structure, miR-324-5p and miR-324-3p, become active miRNAs with distinct targets and functions. (wikipedia.org)
Biomarker2
- MiRNAs are an underexplored potential biomarker and target for treatment for psychiatric disease. (wikipedia.org)
- This evidence comes from laboratory models of AD, as well as living patients, showcasing the potential of neuronal excitability changes as a biomarker for early detection of AD. (nature.com)
Neuroinflammation1
- The goal of our project is to find out whether boosting the physiological process of resolution of neuroinflammation is able to revert the neuronal and behavioral dysfunctions observed in the ASD mouse model. (autism.org)
Cells3
- Binding of a miRNA to a complementary sequence in a target mRNA is mediated by Argonaute proteins leading to degradation of the mRNA or translational inhibition, thereby lowering protein levels in cells [ 7 ]. (researchsquare.com)
- We also found, in separate studies, that microRNA (miRNA) expression in PBMo and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) differed in the IL-1ß/IL-10-based ASD subgroups. (frontiersin.org)
- Sensory ganglia may also have intrinsic interneurons and non-neuronal supporting cells. (lookformedical.com)
Expression4
- Changes in miRNA expression are seen in epileptogenesis and in other disease pathologies. (wikipedia.org)
- The genetic reason for Angelman syndrome is the neuronal lack of UBE3A expression within the mind. (chxa.com)
- ASD subgroup-specific associations were observed between serum miRNA expression and IL-1ß/IL-10 ratios, mitochondrial respiration, and monocyte cytokine profiles (IL-10, CCL2, and TNF-α). (frontiersin.org)
- Circular RNAs (circRNAs) are a class of recently rediscovered ncRNAs with high levels of expression in the brain and proposed roles in diverse neuronal processes. (uni-frankfurt.de)
Onset1
- In this review, we summarize the evidence for neuronal excitability changes over the course of AD onset and progression and the molecular mechanisms underpinning these differences. (nature.com)
Cognitive1
- Furthermore, this group of patients are at risk for comorbidities from unrelenting seizures such as cognitive impairment, and sudden unexpected death (SUDEP). (evolutamente.it)
Mitochondrial1
- Serum miRNA levels were examined by high-throughput deep sequencing in ASD and non-ASD control sera with concurrent measurement of PBMo cytokine production and mitochondrial respiration by PBMCs. (frontiersin.org)
Antisense1
- Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don't respond well to seizure medications. (medscape.com)
Specifically1
- Specifically, miRNA levels were increased and decreased in eight and nine miRNAs, respectively, in the high-ratio ASD subgroup (N = 48). (frontiersin.org)
Genetic1
- We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures," Kaye told Medscape Medical News . (medscape.com)
Death1
- Cell Death & Disease] Using an integrative and comprehensive analysis of the TCGA database and the transcriptome of glioblastoma (GBM) biopsies, the authors identified three critical and clinically relevant miRNAs for GBM, miR-17-3p, miR-222, and miR-340. (stemcellsciencenews.com)
Levels3
- Seizures are characterized by high levels of synchronized neuronal activity. (wikipedia.org)
- Serum miRNA levels differed between the overall ASD sera (N = 116) and non-ASD control sera (N = 35) and also differed across the IL-1ß/IL-10-based ASD subgroups. (frontiersin.org)
- In contrast, the low- (N = 25) and normal- (N = 43) ratio ASD subgroups only showed decreased miRNAs levels (18 and 10 miRNAs, respectively). (frontiersin.org)
Mice2
- Importantly, miR-324-5p has increased association with the RISC complex following seizure in mice, indicating more suppressive activity. (wikipedia.org)
- We now wish to determine whether the miRNA associated with prenatal stress, administered to pregnant mice, recapitulate behavioral (Aim 1), neurochemical (Aim 2), and other epigenetic effects (Aim 3) of prenatal stress exposure, to begin to understand the mechanism. (autism.org)
Function2
Protein1
- Published research demonstrates that this miRNA interacts with the Hedgehog (HH) signaling pathway via interactions with HH transcription factor Gli1 and HH protein receptor Smo, often contributing to tumorigenesis. (wikipedia.org)
Activity1
- One important regulator of neuronal activity is the hyperpolarizing A-type current mediated by potassium channel KV4.2. (wikipedia.org)
Cell1
- method of labeling a neuronal cellular circuit in a neuronal cell. (apslaw.com)
Effects1
- In cascade to ABCD1, lysosomal effects and neuronal Platelets are asymmetric arrows of ALD( Kemp et al. (evakoch.com)