The transcript encoding translationally controlled tumor protein (Tctp), a molecule correlated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis. We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time due to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl-2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that Tctps anti-apoptotic activity is necessary for the normal development of the retinotectal projection. The findings suggest that Tctp supports the development of the retinotectal ...
Pathogenesis of the autoimmune disease multiple sclerosis (MS) is associated with progressive deterioration of the myelin sheath surrounding neuronal axons; however, axon damage may also contribute to MS-associated neurodegeneration. Nikić et al. used in vivo imaging and electron microscopy to examine axon damage in a mouse model of MS (EAE, experimental autoimmune encephalitis). In EAE mice, swelling in discrete sites on axons was observed, which was then followed by axon fragmentation. In many cases, damaged axons retained myelin; in some cases, axon damage was reversible. Axon damage was preceded by mitochondrial pathology, which was associated with the presence of microglia and the production of reactive oxygen and nitrogen species. Induction of oxidative or nitrosative stress was sufficient to induce mitochondrial pathology and axon damage in normal mice, and their blockade in EAE mice alleviated axon damage. Lesion biopsies from MS patients also showed similar axon (above, right) and ...
TY - JOUR. T1 - Dystroglycan is a scaffold for extracellular axon guidance decisions. AU - Lindenmaier, L. Bailey. AU - Parmentier, Nicolas. AU - Guo, Caiying. AU - Tissir, Fadel. AU - Wright, Kevin. PY - 2019/2/13. Y1 - 2019/2/13. N2 - Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events ...
Axonal localization of viral membrane proteins promoted by Us9 missense mutants correlates with degree of anterograde spread in the rodent nervous system. Neuro
The eye is a peripheral outpost of the central nervous system (CNS) where the retinal ganglion cells (RGCs) reside. RGC axons navigate to their targets in a remarkably stereotyped and error-free manner and it is this process of directed growth that underlies the complex organization of the adult brain. The RGCs are the only retinal neurons to project into the brain and their peripheral location makes them an unusually accessible population of projection neurons for experiments involving in vivo gene transfer, anatomical tracing, transplantation and in vitro culture. In this paper, we review recent findings that have contributed to our understanding of some of the guidance decisions that axons make in the developing visual system. We look at two choice points in the pathway, the optic nerve head (onh) and the midline chiasm, and discuss evidence that supports the idea that key molecules in guiding axon growth at these junctures are netrin-1 (onh) and ephrin-B (chiasm). In the optic tectum where RGC axon
zag-1 activity establishes several neuronal characteristics, such as cell position, axonal structure and gene-expression profile. Although zag-1 mutations confer various defects on sensory, motor and interneurons, common or related phenotypes are evident. These include the absence of stereotypic axon branches and upregulation of neurotransmitter biosynthetic and reuptake genes. zag-1 functions less to define neuron identity per se and more to generate features characteristic of a particular type of neuron. The specificity and selectivity of zag-1 phenotypes for each neuron type suggests that zag-1 acts in combination with other cell-type-specific factors to control differentiation.. SRA-6 is a candidate chemosensory receptor, based on its predicted seven transmembrane domain topology and expression in amphid sensory neurons ASH and ASI (Troemel et al., 1995). sra-6::gfp provides an ideal indicator of PVQ development and differentiation, although sra-6 function in interneuron PVQ is unclear. ...
This is a message to people interested (or potentially interested) in the development of the Drosophila motor axon system and CNS: I recently constructed a World Wide Web site (linked to our homepage, which is http://www.caltech.edu/~zinn/ ) on motor axon development in flies. This consists at present of a gallery of high-resolution Photoshop images (,35 images of antibody-stained embryos photographed with DIC optics, and several diagrams) of the neuromuscular system in embryos, with accompanying text. Most of the images in the current version are of wild-type embryos stained with the 1D4 antibody against Fasciclin II, which specifically labels motor axons (Van Vactor et al., Cell 73, 1137-1153 (1993)). The same segments are shown in several focal planes, so that the viewer can see the details of the pathways as if they were examining an actual embryo under the microscope. There are also embryos double-stained for PNS, muscle, and tracheal markers, so that motor axon development can be keyed to ...
In contrast to peripheral nerves, damaged axons of the mammalian brain and spinal cord rarely regenerate. Although the nature of the neuronal environment, particularly inhibitory molecules on myelin and in glial scar tissue, can partially explain the lack of regeneration in the CNS, intrinsic neuronal factors also have an influence. Intrinsic influences on axon growth are neuronal age (Lagunowich et al., 1992; Li et al., 1995), neuronal cell type (Benfey et al., 1985; Rossi et al., 2001), distance of axotomy from the cell body (Fernandes et al., 1999), and conditioning (McQuarrie, 1978; Neumann and Woolf, 1999). Thus, embryonic axons grow through environments that ordinarily block regeneration, some axons mount a vigorous regenerative response whereas some never regenerate, axons cut close to the cell body show a greater regenerative response than those cut more distally, and axons may regenerate with greater vigor if they have been damaged some days previously.. For successful regeneration, the ...
One of the most challenging problems in biology is to understand how the billions of neurons in the mammalian nervous system "wire up" to form functional neural circuits that underlie all behaviour. This has been one of the most intensely studied areas of developmental neurobiology in the past, and a number of important proteins have been identified that instruct axons to project to their specific target regions (so called axon guidance proteins).. Our current work focuses on how axon guidance proteins are detected by receptor proteins on growing axons, how these receptors signal and how they are regulated by for example endocytosis or proteolytic cleavage. Remarkably, our nervous system contains billions of connections but no more than a hundred axon guidance proteins. How can this relatively small number of proteins set up the wiring of a disproportionally large number of connections with many different characteristics such as trajectories or synaptic partners? Evidence is emerging that the ...
Nakamura, T., et al. (2017). Novel role of Rac-Mid1 signaling in medial cerebellar development. Development 144(10): 1863-1875. PubMed ID: 28512198 Nakaya, Y., Kuroda, S., Katagiri, Y. T., Kaibuchi, K. and Takahashi Y. (2004). Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1. Dev Cell. 7(3): 425-38. 15363416 Newsome, T. P., Schmidt, S., Dietzl, G., Keleman, K., Asling, B., Debant, A., and Dickson, B. J. (2000). Trio combines with Dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila. Cell 101: 283-94. PubMed Citation: 10847683 Ng, J., et al. (2002). Rac GTPases control axon growth, guidance and branching. Nature 416: 442-447. 11919635 Ng, J. and Luo, L. (2004). Rho GTPases regulate axon growth through convergent and divergent signaling pathways. Neuron 44: 779-793. 15572110 Ng, J. (2008). TGF-β signals regulate axonal development through distinct Smad-independent mechanisms. Development 135(24): ...
While commissural axons pathways are absent in comm mutants, other aspects of CNS development appear normal, including formation of longitudinal axon pathways, nerve roots, peripheral axon pathways, and peripheral sensory neurons. The mutant phenotype appears to be quite specific to the midline of the CNS, since the pattern for cuticle, segmentation, and muscles are normal. The normal axon projection of the ventral unpaired medial neurons (VUMs) is particularly interesting because the VUM cell bodies are located at the midline and extend growth cones that bifurcate and project away from the midline and toward the intersegmental nerve root. The fact that this happens in a relatively normal fashion in comm mutants suggests that there is no physical barrier preventing growth cones from extending near the midline. Later in embryogenesis, in the absence of commissural axon pathways and their surrounding nonneuronal cells holding the two sides of the CNS together, the CNS starts to unzip as it splits ...
Developing motoneurons in zebrafish embryos follow a stereotyped sequence of axonal outgrowth and accurately project their axons to cell-specific target muscles. During axonal pathfinding, an identified motoneuron pioneers the peripheral motor pathway. Growth cones of later motoneurons interact with the pioneer via contact, coupling, and axonal fasciculation. In spite of these interactions, ablation of the pioneer motoneuron does not affect the ability of other identified motoneurons to select the pathways that lead to appropriate target muscles. We conclude that interactions between these cells during pathfinding are not required for accurate pathway selection ...
Precise spatiotemporal control of axon guidance factor expression is a prerequisite for formation of functional neuronal connections. Although Netrin/Dcc- and Robo/Slit-mediated attractive and repulsive guidance of commissural axons have been extensively studied, little is known about mechanisms controlling mediolateral positioning of longitudinal axons in vertebrates. Here, we use a genetic approach in zebrafish embryos to study pathfinding mechanisms of dopaminergic and neuroendocrine longitudinal axons projecting from the hypothalamus into hindbrain and spinal cord. The transcription factors Sim1a and Arnt2 contribute to differentiation of a defined population of dopaminergic and neuroendocrine neurons. We show that both factors also control aspects of axon guidance: Sim1a or Arnt2 depletion results in displacement of hypothalamo-spinal longitudinal axons towards the midline. This phenotype is suppressed in robo3 guidance receptor mutant embryos. In the absence of Sim1a and Arnt2, expression ...
This study will use two-photon cellular imaging in an animal model of human multiple sclerosis (MS) to determine how neural-immune interactions may damage the nerve cells communication cables (axons) to produce disabling cognitive and motor disabilities. MS afflicts about 400,000 people in this country. It is an "autoimmune" disease in which the bodys immune cells mistake as foreign and attack some tissues in the brain and especially in the spinal cord (central nervous system, CNS). MS specifically targets a nerve cells axon and the myelin sheath that covers it. Axons carry nerve cell messages from one cell to another. Just how immune cells inflict damage to axons, however, is not yet known. The investigators hypothesize that "innate" immune cells, the bodys first line of defense, ordinarily help maintain the equilibrium of axons. But in autoimmune inflammation, they turn deadly and fatally injure axons. Since it is not currently feasible to image nerve-immune cell interactions in MS ...
This study will use two-photon cellular imaging in an animal model of human multiple sclerosis (MS) to determine how neural-immune interactions may damage the nerve cells communication cables (axons) to produce disabling cognitive and motor disabilities. MS afflicts about 400,000 people in this country. It is an "autoimmune" disease in which the bodys immune cells mistake as foreign and attack some tissues in the brain and especially in the spinal cord (central nervous system, CNS). MS specifically targets a nerve cells axon and the myelin sheath that covers it. Axons carry nerve cell messages from one cell to another. Just how immune cells inflict damage to axons, however, is not yet known. The investigators hypothesize that "innate" immune cells, the bodys first line of defense, ordinarily help maintain the equilibrium of axons. But in autoimmune inflammation, they turn deadly and fatally injure axons. Since it is not currently feasible to image nerve-immune cell interactions in MS ...
Topographical maps of neuronal connectivity occur in various brain regions. RGC axons have been shown to substantially overshoot their appropriate TZs along the AP axis of the optic tectum/SC during the development of the visual system in chicks and rodents. RGC axons from a given DV location are also broadly distributed along the DV (or mediolateral) tectal axis with a peak in axon density around the proper DV location of the TZ (Simon and OLeary, 1992a, 1992b, 1992c; Hindges et al., 2002). Topographically appropriate connections are then established by selective branching formed along the axon shaft with a bias at the AP location of their future TZ (Simon and OLeary, 1992a; Yates et al., 2001) and preferential extension toward the TZ along the DV axis (Nakamura and OLeary, 1989; Hindges et al., 2002; McLaughlin et al., 2003a). Thus, the target position-specific branching of RGC axons on the tectum is essential to establish a topographic retinotectal map. However, the molecular mechanisms ...
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Nervous system-specific eve mutants were created by removing regulatory elements from a 16 kb transgene capable of complete rescue of normal eve function. When transgenes lacking the regulatory element for either RP2+a/pCC, EL or U/CQ neurons were placed in an eve-null background, eve expression was completely eliminated in the corresponding neurons, without affecting other aspects of eve expression. Many of these transgenic flies were able to survive to fertile adulthood. In the RP2+a/pCC mutant flies: (1) both RP2 and aCC showed abnormal axonal projection patterns, failing to innervate their normal target muscles; (2) the cell bodies of these neurons were positioned abnormally; and (3) in contrast to the wild type, pCC axons often crossed the midline. The Eve HD alone was able to provide a weak, partial rescue of the mutant phenotype, while both the Groucho-dependent and -independent repressor domains contributed equally to full rescue of each aspect of the mutant phenotype. Complete rescue ...
They are caused by gene mutations that happen in abnormalities in the synthesis or catabolism of proteins, carbohydrates, or fats. The DRG contain pseudounipolar sensory neurons В- so called because they furnish arise to a individual axon that bifurcates, with one involvement projecting to the boundary and the other projecting to the dorsal horn of the spinal cord. Carrots check beta-carotene and former carotenoids cheap 0.18mg alesse with mastercard birth control lawsuit. Furthermore, uncountable of the ocular tissues and fluids collected in bioanalytical studies are present in such low amount or substance that reanalysis may be unaccommodating or unachievable, depending on the assay approach utilized. A Ladd returns is performed, during which the intestine is straightened out and bands contributing to the misalignment are divided. Heart disease and the incendiary activity dapoxetine 30mg online erectile dysfunction medication non prescription. The use of such instruments to right off the bat ...
Neurons are polarized cells with axons (the site of signal output) and dendrites (the sites of signal input). Not only are these functionally different parts of the cell, but the morphology of axons and dendrites is very different as well. Two groups report that glycogen synthase kinase 3β (GSK-3β) is at the center of a process that regulates the balance of axons and dendrites. Jiang et al. and Yoshimura et al. reported that when GSK-3β activity was increased by transfection of isolated embryonic hippocampal neurons with a constitutively active mutant, the number of cells that formed an axon or extended neurite was decreased, and when GSK-3β activity was inhibited, using multiple methods, the number of cells producing multiple axons increased. The overall number of neurites was unchanged. Inhibition of GSK-3β activity in cultured neurons before or after polarity had been established produced an increase in the number of cells with multiple axons, suggesting a role for GSK-3β in both ...
Its not as rear as you make it out. Its quite common in SMA and SBMA and some muscular disorders to fasciculate well in advance of weakness or EMG changes. Ive know people that Ive talked with that twitched in their teens only later to be diagnosed with ALS, in-approrpriately, then diagnosis changed to another MND 30 years later. I may be one of them. Ive yet to show changes but Ive been told even after 20 years, Im not out of woods. Not by Dr. Google...or vet....etc. Ive had every test you can imagine, all negative, but still Im a very interesting subject because I fasciculate and have an elevated CPK for 20+ years. Nothing sinister on EMG. But I still see a neurologist. They want to run tests that my insurance company wont pay for....I wont do it unless my Son or Daughter show changes...Lately, my son started to fasciculate and his hands and feet are cramping..might be time to do more tests ...
Yuanyuan (Kevin) Liu has been awarded an American Heart Association Predoctoral Fellowship for his research. Yuanyuan is a graduate student in Biological Sciences in Professor Ben Szaros lab. The funding is for 2 years with a $20,000/yr stipend. The title of his award is: "Studies of an RNA binding protein and its mRNA targets during central nervous system axon regeneration." Of 115 proposals received, Yuanyuans was among the top 6 percent. More specific details about Yuanyuans study may be found below. After a stroke, patients frequently recover only partially due to the disruption of connections between neurons. In the human brain, axons which mediate these connections, generally fail to regenerate beyond the lesion site. In contrast, injured central nervous system neurons in lower vertebrates, such as the frog, can often fully regenerate. Yuanyuan Liu is using the regenerating optic nerve of the frog Xenopus laevis as a model system to study the mechanisms of successful central nervous ...
Nitric oxide gets neurons together. And it seems to do it backward. Work by Nikonenko et al. suggests that a protein called PSD-95 prompts nitric oxide release from postsynaptic dendritic spines, prompting nearby presynaptic ...
Hi there, Currently, when I use maven to build the project I have this problem. I have 2 projects: desk_post and desk_post_test (required desk_post) When I run for desk_post -> mvn clean install -> successful -> created: desk_post-1.00.08.00-SNAPSHOT.iar -> the resources folder alread...
SCOTTSDALE, Ariz., Dec. 1, 2016 /PRNewswire/ -- New Axon Signal Magazine Connects TASER Smart Weapons To Wearable Cameras. The Signal Performance Power...
New research sheds light on the molecular mechanisms underlying axon g...A group led by Michael Hengartner from the University of Zurich in Sw...Hengartner and colleagues then show that UNC-69 physically interacts w...It is known that UNC-76 binds to molecular motor proteins called kin...The short coiled-coil domain-containing protein UNC-69 cooperates with...,Newly,identified,protein,complex,sheds,light,on,axon,growth,mechanism,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
The computational model of in vivo sharp-wave ripples with place cell replay. Excitatory post-synaptic potentials at dendrites gate antidromic spikes arriving from the axonal collateral, and thus determine when the soma and the main axon fire. The model allows synchronous replay of pyramidal cells during sharp-wave ripple event, and the replay is possible in both forward and reverse directions ...
Principal Investigator:MASU Masayuki, Project Period (FY):2010-04-01 - 2015-03-31, Research Category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Project Area:Neural Diversity and Neocortical Organization
The cerebral cortex is essential for all sorts of processing of sense data and motor control. It is where the reasoning and cognition specific to humans (and, to a lesser degree, some other animals) takes place, and is the seat of planning and language, volitional behavior and conscious perceptions, thinking and memory. It is the command center where input sensory information is translated into output motor control. In evolutionary terms, it is the most recently developed part of our brains and has taken over or added to function of older structures.. Its unique and fairly uniform structure (sometimes termed "canonical") allows for great plasticity in functioning. It consists of layers1)Six, in the striate cortex.. of gray matter (neuron cells, dendrites and synapses) on the outside (distally) and white matter (axons) beneath, although the difference in colors is less pronounced than those terms may imply. It consists of two lateral hemispheres joined by a bundle of axonal connections, the ...
There is accumulating evidence that RelA is crucial for axon formation during embryonic neural development (Gavaldà et al., 2009). In cervical superficial ganglia, enhanced site-specific Ser536 phosphorylation of RelA in the presence of p50 impairs increases in neurite length and complexity (Gutierrez et al., 2008), whereas RelA suppression by overexpression of either p50 or a dominant-negative IκBα super-repressor in newborn hippocampal neurons results in complete growth arrest (Imielski et al., 2012). It has been suggested that modification of both IκBα and activated RelA determines a functional switch from growth inhibition to growth promotion (Gavaldà et al., 2009; Gutierrez et al., 2008). Moreover, as recently exemplified for hippocampal neurogenesis, the balance between transactivation-competent and -incompetent NF-κB subunits might also be crucial for axogenesis (Imielski et al., 2012). However, such previous experiments were based on in vitro analysis of premature PNS and newborn ...
GO:0048846. The long distance growth of a single cell process, that is involved in the migration of an axon growth cone, where the migration is directed to a specific target site by a combination of attractive and repulsive cues. ...
Slit1 triggers Netrin-1 repulsion for hippocampal neurons on PLL-coated substrate. (A) Last brighfield images of typical growing axons on PLL-coated microwells.
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The purpose of this book is to provide a straightforward but thorough introduction to accounting and finance for executives and managers who are studying these subjects, formally, for the first time. It is an entry-level text to be used before moving on to more advanced material. A high degree of practicality and relevance are introduced with a strong real world flavour supported by examples from leading international companies. The glossary of terms is designed to be as comprehensive as possible so that readers can obtain clear guidance at a time when they most need it.... ...
Paul Joseph Watson covers the latest Ebola news and plays a clip where the partner of the Ebola infected man says the CDC has not given her any guidance at all.. ...
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We show that the perceptual experience of retinal implant users can be accurately predicted using a computational model that simulates each individual patients retinal ganglion axon pathways ...
During the GEF-6 replenishment, the focal area strategies were designed to meet specific measured by key indicators. After one year of GEF-6 programming in which 20.4 percent of GEF-6 resources were programmed, the planned expected results among approved projects in five of the ten target areas were already close to or beyond the 50 percent mark in the programming of the overall planned expected results of the target area. It should be noted though, that these data are based on expected, not actual results, which will only materialize as implementation progresses.. ...
REGULATION OF AXONAL DEVELOPMENT BY THE cGMP SIGNALING PATHWAY By Zhen Zhao A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirement for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2009 Copyright 2009 Zhen Zhao ii Acknowledgements I would like to express my gratitude to all those who assisted me to complete my work and this thesis. I want to thank University of Southern California, Neuroscience Graduate Program and Zilkha Neurogenic Institute for giving me the opportunity to pursue my doctoral degree. I am deeply indebted to my supervisor Prof. Dr. Le Ma. It was his guidance, encouragement, suggestions and full support that made this work possible. I also have to thank my committee members, Dr. Samantha Buttler, Dr. James Knowles, Dr. Emily Liman, Dr. David Mckemy, Dr. Zuo-zhong Wang and Dr. Qilong Ying for their valuable help, and Dr. Li Zhangs lab, Dr. Jonah Chan and Dr, Zuo-zhong Wangs lab for ...
REGULATION OF AXONAL DEVELOPMENT BY THE cGMP SIGNALING PATHWAY By Zhen Zhao A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirement for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2009 Copyright 2009 Zhen Zhao ii Acknowledgements I would like to express my gratitude to all those who assisted me to complete my work and this thesis. I want to thank University of Southern California, Neuroscience Graduate Program and Zilkha Neurogenic Institute for giving me the opportunity to pursue my doctoral degree. I am deeply indebted to my supervisor Prof. Dr. Le Ma. It was his guidance, encouragement, suggestions and full support that made this work possible. I also have to thank my committee members, Dr. Samantha Buttler, Dr. James Knowles, Dr. Emily Liman, Dr. David Mckemy, Dr. Zuo-zhong Wang and Dr. Qilong Ying for their valuable help, and Dr. Li Zhangs lab, Dr. Jonah Chan and Dr, Zuo-zhong Wangs lab for ...
Immature motoneurons are highly susceptible to degeneration following axon injury. The response of perineuronal glia to axon injury may significantly influence neuronal survival and axon regeneration. We have examined the central reactions to neonatal facial nerve transection with emphasis on the expression of complement component C3 (C3) and the multifunctional apolipoprotein J (ApoJ). Axotomy was performed on one-day-old rats. Animals were perfused from eight hours to two weeks after the lesion. The astroglial marker, glial fibrillary acidic protein (GFAP) was increased from one day and the microglial marker OX-42 from two days after injury. ApoJ immunoreactivity was increased in axotomized neuronal perikarya and astroglial cells from one day postaxotomy, but no C3 immunoreactive profiles were found at any postoperative survival time. Cell proliferation as judged by bromodeoxyuridine labeling and immunoreactivity for the cyclin Ki-67 antigen (antibody MIB5) occurred only at two days after ...
In contrast to the central nervous system (CNS) nerve fibers do regenerate in the peripheral nervous system (PNS) although in a clinically unsatisfying manner. A major problem is excessive sprouting of regenerating axons which results in aberrant reinnervation of target tissue and impaired functional recovery. In the CNS, the reticulon protein Nogo-A has been identified as a prominent oligodendrocyte expressed inhibitor of long-distance growth of regenerating axons. We show here that the related isoform Nogo-B is abundantly expressed in Schwann cells in the PNS. Other than Nogo-A in oligodendrocytes, Nogo-B does not localize to the myelin sheath but is detected in the ER and the plasma membrane of Schwann cells. Adult sensory neurons that are cultured on nogo-a/b deficient Schwann cells form significantly fewer axonal branches versus those on wildtype Schwann cells, while their maximal axonal extension is unaffected. We demonstrate that this effect of Nogo-B on neuronal morphology is restricted to
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Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated predominantly with small-caliber nerve fibers. Similar swellings were absent in dysmyelinated shiverer mice, which lack myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber degeneration, which was probably secondary to impaired axonal transport, could indicate that myelinated axons require local oligodendroglial support. ...
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We recently noted, in performing a metabolic characterization of mice deleted for LKB1 in the endocrine pancreas and a restricted set of CNS neurons using a RIP2-Cre transgene (Sun et al., 2010b), that older animals became paralyzed. The principal aim of the present study was thus to dissect the pathology behind this change and, in doing so, to determine the role of LKB1 in regulating neuronal polarity and survival in the CNS in vivo.. Although mice null for LKB1 throughout the body die before E11.5, the use of an Emx1-Cre deleter strain to allow deletion in pyramidal neuron progenitors demonstrated that LKB1 is required for the polarization of cultured neurons from the neonatal hippocampus and cortex (Barnes et al., 2007; Shelly et al., 2007). We therefore reasoned that LKB1 might play a similar role in axon development and, importantly, in signal transmission along the spinal cord. Given the crucial role of the spinal cord for the normal control of motor function, we further reasoned that ...
This allowed us to systematically investigate how metabolic cost depends on factors such as axonal geometry and ion channel densities. E.g comparing myelinated and unmyelinated axons with the same axon diameter of 1µm (fibre diameter including myelin sheath was 3.7 µm) we find the following: single APs at a myelinated axons Node of Ranvier have a metabolic cost of 3.5 pmol/cm² ATP per unit membrane area. This is approximately 7 times the amount per AP in hippocampal mossy fibre (0.53 pmol/cm2;[2]) but less than leaky squid axons (5 pmol/cm2). However, Node of Ranvier cover only 0.33% in our myelinated axon. The internodal regions contain hardly any Na+ channels, but a low density of K+ channels (3 µm-2) along internodes, and higher densities at the paranode (80 µm-2). We estimate overall energy consumption based on Na currents at the Node and K along a segment comprising half the internodal fibre on both sides of a node. This yields an AP cost per myelinated axon segment of 0.05 pmol/cm2 ...
Histology in DAI. A number of histological techniques are available to appreciate sequential pathological changes in axons in diffuse axonal injury. These are primarily aimed at shortening the duration at which the axonal changes are seen and to put them in context to various traumatic and non traumatic conditions so as to differentiate the causative mechanism. Axonal swellings or retraction balls, representing transected axons, are the histological hallmark of axonal injury but are usually not visible before 24 to 36 hours by routine H & E staining or with a myelin stain like Luxol fast blue [2]. Silver staining method can reliably demonstrate axonal swellings within 12 to 18 hours [27]. The method has been found to be more sensitive and reliable as compare to H & E staining. However diffuse staining of axons by silver stains may occasionally make differentiation of injured and irregular axons difficult thereby limiting their practical utility [28]. Injuries to the axons may be detected even ...