Download or read book Investigating Molecular Mechanisms of Neuronal Regeneration written by Alison Margaret Blain and published by . This book was released on 2009 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: Injury to the peripheral nervous system (PNS) stimulates a finely regulated regenerative response that generally leads to some recovery of function. In contrast, the response to injury in the adult mammalian central nervous system (CNS) is abortive and adult CNS neurons do not normally regenerate. We used a microarray approach to identify putative regeneration-associated changes in gene expression in the L4 dorsal root ganglion (DRG) in rat models of PNS and CNS injury. Our models included crush injury to both branches of the bifurcating axon of sensory neurons with cell bodies in the DRG (DRGNs). Injury to the peripheral branch at the level of the spinal nerve (SN) results in axonal regeneration and reinnervation. Crush injury of the central branch in the dorsal root (DR) results in active regeneration up to the point of CNS entry at the DR entry zone (DREZ) and subsequent arrest of further growth, while transection injury within the CNS at the level of the dorsal columns (DC) results in abortive and unsuccessful regeneration attempts. These DRGN injury models therefore allowed us to compare the gene expression programmes elicited during active, arrested and abortive regeneration. Following a pilot microarray experiment to optimize experimental parameters and tract tracing and electrophysiological experiments to confirm time points for harvest of DRGs after DR and SN injury, respectively, male Sprague-Dawley rats underwent an L4 SN crush, an L4 DR crush or a bilateral DC transection at the L3/L4 spinal segment boundary. L4 DRGs were collected at 2 weeks (active regeneration) and 6 weeks (arrested regeneration) after DR crush. DRGs were harvested at 6 weeks after SN crush and 2 weeks after DC transection. DRGs harvested from naïve rats served as a control group. Microarray analysis (Affymetrix Rat genome 230 2.0 array) identified several hundred genes showing differential expression (5% FDR) in comparisons of regenerating with non-regenerating conditions. Selected genes were chosen for validation by qRT-PCR. These genes could represent putative regeneration-associated genes and may suggest novel therapeutic interventions to encourage regeneration of the spinal cord following injury. Additionally, we have identified genes upregulated in the DR active regeneration state relative to DR arrested state, which have relevance to root avulsion injury and may provide insight into the mechanisms that prevent regeneration of DR axons through the DREZ to re-enter the spinal cord. We also present evidence that a transcriptional programme consistent with regeneration is mounted within the DRG following DC transection. This lends support to the idea that CNS neurons have intrinsic regenerative capability and that manipulations of the CNS environment may be sufficient to permit regeneration of CNS axons.

Download or read book Investigation of the Molecular Mechanisms of Dendrite Regeneration written by Richard Mayo Albertson and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurons are highly polarized cells that have an axon and dendrite component. Axons function to transmit information away from the neuron, while dendrite typically bring information to the neuron. Most neurons face the daunting challenge of needing to survive a lifetime, as the vast majority of neurons are not replaced by a stem cell population in adulthood. However, neurons also face many risks from a wide range of insults. Neurons that survive these insults often suffer from damaged axons or dendrites that may hinder function. Regeneration of lost axons or dendrites represents an important strategy for recovering from these injuries. Axon regeneration has been studied for over 150 years, yet dendrite regeneration is only beginning to be recognized as a relevant neuronal process. Dendrite regeneration is a recently discovered neuronal injury response that is only now beginning to be understood. In Chapter 2, data will be presented that demonstrates dendrite regeneration restores mature and functional dendrites in Drosophila sensory neurons. Data will also be presented on a candidate RNAi screen that highlights the challenge of identifying genes required for dendrite regeneration, as little information is gleaned from this approach. Techniques now exist that allow investigation of the entire genome and transcriptomes of cells. In Chapter 3, a functional genomics approach is used to identify novel regulators of dendrite regeneration. By combining RNA sequencing from injured Drosophila sensory neurons to a targeted RNAi screen, genes are identified whose knockdown results in decreased dendrite regeneration. Genes are identified in dendrite regeneration that cover a wide range of molecular signaling function including transcription factors, tyrosine kinase signaling components, cell surface receptors, and kinetochore associated proteins. Receptor tyrosine kinases (RTKs) are a class of transmembrane receptors well known for roles in transducing signals from the extracellular environment into the cell. The Ror family of RTKs is one family that has well described roles for development of the nervous system in C. elegans and mammals. While Drosophila have two Ror family RTKs, virtually nothing is known about the function of these genes in Drosophila neurons. In Chapter 4, it is shown that Ror is required for dendrite regeneration in Drosophila ddaC and ddaE peripheral sensory neurons. It is also shown that Ror is required neither for normal dendrite development nor for axon regeneration. Data is shown that suggests Ror may be acting in a Wnt signaling pathway and contributing to -tubulin localization to dendritic branch points, and that this may be the underlying mechanism for the role of Ror in dendrite regeneration.

Download or read book Neural Plasticity and Memory written by Federico Bermudez-Rattoni and published by CRC Press. This book was released on 2007-04-17 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq

Download or read book Investigating the Molecular Mechanisms of Axon and Dendrite Regeneration in Drosophila Peripheral Neurons written by Rachel Swope and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurons must endure the lifetime of an organism, but their axons and dendrites are vulnerable to insults, including stoke, neurodegenerative disease, traumatic injuries to the brain and spinal cord, anticancer drugs, and infection. Neurons in the PNS have evolved robust mechanisms to regenerate a damaged axon or dendrite(s). Molecular mechanisms for dendrite regeneration remain undefined, so I performed a candidate-based screen of protein traps and Gal4-enhancer traps to find a reporter for dendrite regeneration. I also studied how plasma membrane (PM) expansion is polarized during axon regeneration. Smooth endoplasmic reticulum (SER) is enriched at the tip of regenerating axons but not regenerating dendrites, so I hypothesized that the SER is a site of local lipid synthesis here and adds lipids to the PM via non-vesicular transport at membrane contact sites. The alternate hypothesis is that the bulk of new PM is added via Exocyst-dependent polarized secretion of post-Golgi vesicles. SER could provide Ca2+ to trigger the fusion of these vesicles with the PM at the regenerating axon tip. I found that the ER-PM lipid transfer protein, extended synaptotagmin 2 (ESyt2), is not enriched in the SER at the tip of the regenerating axon. Instead, I found that the Exocyst complex is essential for axon regeneration and several other forms of neurite outgrowth. My findings support the hypothesis that most new PM comes from Exocyst-dependent secretion of post-Golgi vesicles rather than non-vesicular lipid transfer at ER-PM membrane contact sites.

Download or read book Translational Research in Traumatic Brain Injury written by Daniel Laskowitz and published by CRC Press. This book was released on 2016-04-21 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt: Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

Download or read book Molecular Mechanisms of Neural Plasticity After Spinal Cord Injury in the Lamprey Central Nervous System written by Billy You Bun Lau and published by . This book was released on 2012 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Spinal cord injury induces anatomical plasticity throughout the nervous system, including distant locations in the brain. Several types of injury-induced plasticity have been identified, such as neurite sprouting, axon regeneration and synaptic remodeling. However, the molecular mechanisms involved in anatomical plasticity after injury are unclear, as is the extent to which injury-induced plasticity in the brain is conserved across vertebrate lineages. Here, I used lampreys to identify the molecular mechanisms in mediating anatomical plasticity, because lampreys undergo anatomical plasticity and functional recovery after a complete spinal cord transection. Due to their robust roles in neurite outgrowth during neuronal development, I examined synapsin and synaptotagmin for their potential involvement in anatomical plasticity after injury. I found increased synapsin I mRNA throughout the lamprey brain as well as increased protein levels of synapsin I, phospho-synapsin (Ser 9) and synaptotagmin in the lamprey hindbrain after injury, suggestive of anatomical plasticity. Anatomical plasticity was confirmed at the ultrastructural level, where I found increased neurite density in the lamprey hindbrain after injury. Other molecular mechanisms that promote anatomical plasticity have been previously identified, such as cyclic AMP (cAMP). However, the cellular mechanisms and the molecular targets of cAMP in mediating anatomical plasticity are unclear. My investigation of cAMP revealed that cAMP enhanced the number of regenerated axons beyond the lesion site in lampreys after injury. For the first time in a spinal cord injury model, I found cAMP prevented the death of axotomized neurons that normally have a high tendency to die after injury. In addition, cAMP promoted more regenerating axons to re-grow in straighter paths rather than turning rostrally towards the brain stem. At the molecular level, I found cAMP increased synaptotagmin protein level at the regenerating axon tips, suggestive of enhanced axon elongation. Taken together, my results show that neurite sprouting in the brain and the cAMP-enhanced axon regeneration are conserved responses in vertebrates after spinal cord injury. In addition, my results suggest that at least some developmental pathways are activated during injury-induced and cAMP-enhanced anatomical plasticity. Further understanding of these pathways will provide insights for improving recovery after spinal cord injury.

Download or read book Molecular Mechanisms in Brain Regeneration written by Bipin Abhipradnya and published by . This book was released on 2023-10-30 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Mechanisms of Regeneration in the Central Nervous System written by Jeannette Ellen Prentice and published by . This book was released on 1996 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Cajal s Degeneration and Regeneration of the Nervous System written by Santiago Ramón y Cajal and published by History of Neuroscience. This book was released on 1991 with total page 977 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a reprint of an English translation of Cajal's original work, with abundant notes and commentaries by the editor. This text describes Cajal's fundamental contributions to neuroscience, which continue to be important today. It accurately details Cajal's ideas and data, and providesreaders with the opportunity to learn what Cajal thought about his research career and the significance of his observations. Excerpts from Tello's memorial lectures also provide a contemporary view of Cajal's work.

Download or read book Molecular Mechanisms of Myelin Dysfunctions in the Nervous System written by Jihyun Kim and published by . This book was released on 2017 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is generated by Schwann cells (SCs) in the peripheral nervous system (PNS) and by oligodendrocytes (OLs) in the central nervous system (CNS). Myelin not only provides physical and structural support to the axon, it also provides trophic and metabolic supports. In addition, myelin is important for rapid nerve conduction, which is essential for proper communication within a neuronal circuit. Therefore, damage to myelin or myelin loss disrupts axonal integrity and impairs neuronal functions. Elucidating molecular mechanisms underlying myelin defects under pathological conditions will be important in gaining insights into developing a strategy for preventing myelin loss and improving myelin repair. In this study, we investigated molecular mechanisms of aberrant myelination and myelin loss associated with Charcot Marie Tooth disease (CMT) in the PNS and traumatic brain injury (TBI) in the CNS. In Chapter 1, we investigated the impact of CMT4B1-associated MTMR2 loss in SCs. CMT4B1 is a genetically inherited disorder of the PNS that is caused by loss of MTMR2 gene function. In CMT4B1 patients, myelin outfolding and demyelination are observed resulting in decreased nerve conduction, muscle weakness, atrophy, and sensory deficits. Previously, it has been shown that SC-specific deletion of MTMR2 in mice results in reduced nerve conduction and myelin abnormalities similar to defects observed in CMT4B1patients. However, the mechanism(s) by which loss of MTMR2 function leads to the myelin abnormalities are not fully understood. To elucidate the underlying mechanisms, we generated MTMR2 knockdown SCs and analyzed the effect of MTMR2 loss on intracellular signaling pathways that are essential for SC myelination. Since MTMR2 is a phosphoinositide 3-phosphatase that regulates the PI(3,5)P2 metabolism, it is possible that abnormal regulation of the PI(3,5)P2 level in MTMR2 KD SCs may be associated with the aberrant SC functions. Recently, PI(3,5)P2 has been shown to serve as a platform for mTORC1 signaling on lysosomal membrane. Since mTORC1 has an important role in SC myelination, we monitored whether MTMR2 loss affects the mTORC1 signaling pathway in SCs. Here, we report an aberrant increase in mTORC1 activity in MTMR2 KD SCs. The mTORC1 activation is also associated with inhibition of autophagy and transcription activity of TFEB, a regulator of lysosomal biogenesis and function. Myelin repair or promoting remyelination in the PNS is important for improving neuronal function in patients with peripheral myelin dysfunctions. In Chapter 2, we elucidated the promyelination function of recombinant TIMP-3 in SCs. TIMP-3 is a member of the tissue inhibitor of metalloproteinase family proteins and one of the targets includes ADAM17. Endogenous ADAM17 in the PNS negatively regulate axonal Nrg1 type III signaling that is essential for SC myelination. Here, we report that recombinant TIMP-3 enhances myelin formation by SCs. The TIMP-3 function is associated with an increase in axonal Nrg1 signaling and laminin deposition during the early stages of myelin formation. In Chapter 3, we investigated molecular mechanisms underlying myelin dysfunction in the CNS associated with TBI. Myelin loss following TBI contributes to axonal degeneration, neuronal death and in long-term, neuronal dysfunction in the patients. Recent studies provide evidence that primary myelin loss contributes to the myelinated axon pathology following TBI. The myelin loss appears to occur without OL death, indicating that demyelination results from a mechanism that actively destroys myelin in viable OLs. Therefore, understanding the mechanisms of OL response to injury may provide insights into preventing demyelination and/or to protecting proper axon- myelin units following TBI. To this end, we investigated the direct impact of mechanical injury on OLs. We developed an OL monoculture system established on a deformable silicone membrane that can be rapidly stretched by a computer-controlled air pulse, which mimics diffused mechanical injury in the brain following TBI. Our data show that stretch injury induces activation of the Erk1/2 pathway in OLs, which leads to myelin protein loss. Furthermore, the Erk1/2 activation was induced by intracellular calcium increase. Inhibition of Erk1/2 or chelating intracellular calcium prevents myelin protein loss after stretch injury. Furthermore, TBI in vivo results in rapid Erk1/2 activation in white matter OLs accompanied by losing the mature OL phenotype. By studying the molecular mechanisms responsible for myelin malformation or myelin loss in demyelinating diseases, we provide evidences of signaling pathways or signaling molecules that could be potential therapeutic targets for preventing myelin dysfunctions.

Download or read book Neuronal Networks in Brain Function CNS Disorders and Therapeutics written by Carl Faingold and published by Academic Press. This book was released on 2013-12-26 with total page 537 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics, edited by two leaders in the field, offers a current and complete review of what we know about neural networks. How the brain accomplishes many of its more complex tasks can only be understood via study of neuronal network control and network interactions. Large networks can undergo major functional changes, resulting in substantially different brain function and affecting everything from learning to the potential for epilepsy. With chapters authored by experts in each topic, this book advances the understanding of: - How the brain carries out important tasks via networks - How these networks interact in normal brain function - Major mechanisms that control network function - The interaction of the normal networks to produce more complex behaviors - How brain disorders can result from abnormal interactions - How therapy of disorders can be advanced through this network approach This book will benefit neuroscience researchers and graduate students with an interest in networks, as well as clinicians in neuroscience, pharmacology, and psychiatry dealing with neurobiological disorders. - Utilizes perspectives and tools from various neuroscience subdisciplines (cellular, systems, physiologic), making the volume broadly relevant - Chapters explore normal network function and control mechanisms, with an eye to improving therapies for brain disorders - Reflects predominant disciplinary shift from an anatomical to a functional perspective of the brain - Edited work with chapters authored by leaders in the field around the globe – the broadest, most expert coverage available

Download or read book Peripheral Nerve Regeneration written by Giovanna Gambarotta and published by Frontiers Media SA. This book was released on 2019-12-24 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Indwelling Neural Implants written by William M. Reichert and published by CRC Press. This book was released on 2007-12-17 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite enormous advances made in the development of external effector prosthetics over the last quarter century, significant questions remain, especially those concerning signal degradation that occurs with chronically implanted neuroelectrodes. Offering contributions from pioneering researchers in neuroprosthetics and tissue repair, Indwel

Download or read book The Aging Mind written by National Research Council and published by National Academies Press. This book was released on 2000-04-18 with total page 285 pages. Available in PDF, EPUB and Kindle. Book excerpt: Possible new breakthroughs in understanding the aging mind that can be used to benefit older people are now emerging from research. This volume identifies the key scientific advances and the opportunities they bring. For example, science has learned that among older adults who do not suffer from Alzheimer's disease or other dementias, cognitive decline may depend less on loss of brain cells than on changes in the health of neurons and neural networks. Research on the processes that maintain neural health shows promise of revealing new ways to promote cognitive functioning in older people. Research is also showing how cognitive functioning depends on the conjunction of biology and culture. The ways older people adapt to changes in their nervous systems, and perhaps the changes themselves, are shaped by past life experiences, present living situations, changing motives, cultural expectations, and emerging technology, as well as by their physical health status and sensory-motor capabilities. Improved understanding of how physical and contextual factors interact can help explain why some cognitive functions are impaired in aging while others are spared and why cognitive capability is impaired in some older adults and spared in others. On the basis of these exciting findings, the report makes specific recommends that the U.S. government support three major new initiatives as the next steps for research.

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Mechanisms of Neuronal Responsiveness written by Yigal H. Ehrlich and published by Springer Science & Business Media. This book was released on 2013-03-13 with total page 553 pages. Available in PDF, EPUB and Kindle. Book excerpt: The interaction of neurotransmitters, neuromodulators and neuroactive drugs with receptors localized at the cell surface initiates a chain of molecular events leading to integrated neuronal responses to the triggering stimuli. Major advancements in the characterization and isolation of recep tor molecules have answered many quest ions regarding the nature of the ele ments that determine the specificity in these interactions. At the same time, recent studies have provided evidence that delicate regulation by intracellular enzymatic systems determines the efficiency of the stimulus response coupling process, mediates the interaction between receptors, operates in feedback control mechanisms and transduces signals from the receptors to various effector sites in a highly coordinated fashion. These studies are at the focus of the present volume, which is an outcome of a symposium held at the University of Vermont College of Medicine on March 21-23, 1986, in conjunction with the seventeenth annual meeting of the Amer ican Society for Neurochemistry. The symposium has demonstrated clearly that the concerted efforts of investigators in neurophysiology, biochemis try, pharmacology, cell-biology, molecular genetics, neurology, and psy chiatry are required to achieve better understanding of the processes under lying neuronal responsiveness. This volume includes contributions provided by prominent investigators in all these research areas. We hope that the readers will find here a useful source of information and ideas for stimu lating further studies which may serve to narrow the gap between basic neuroscience research and its clinical implications.

Download or read book Core Topics in Neuroanaesthesia and Neurointensive Care written by Basil F. Matta and published by Cambridge University Press. This book was released on 2011-10-13 with total page 535 pages. Available in PDF, EPUB and Kindle. Book excerpt: Core Topics in Neuroanesthesia and Neurointensive Care is an authoritative and practical clinical text that offers clear diagnostic and management guidance for a wide range of neuroanesthesia and neurocritical care problems. With coverage of every aspect of the discipline by outstanding world experts, this should be the first book to which practitioners turn for easily accessible and definitive advice. Initial sections cover relevant anatomy, physiology and pharmacology, intraoperative and critical care monitoring and neuroimaging. These are followed by detailed sections covering all aspects of neuroanesthesia and neurointensive care in both adult and pediatric patients. The final chapter discusses ethical and legal issues. Each chapter delivers a state-of-the art review of clinical practice, including outcome data when available. Enhanced throughout with numerous clinical photographs and line drawings, this practical and accessible text is key reading for trainee and consultant anesthetists and critical care specialists.