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Author: Karun K. Singh Publisher: ISBN: 9780494579275 Category : Languages : en Pages : 382
Book Description
The formation of neural connections in the mammalian nervous system is a complex process. During development, axons are initially overproduced and compete for limited quantities of target-derived growth factors. Axons which participate in functional circuits and secure appropriate amounts of growth factors are stabilized, while those axons that are either inappropriately connected or do not obtain sufficient concentrations of growth factors are eliminated in a process termed 'axon pruning'. In this thesis, I examined the mechanisms that regulate pruning of peripheral, NGF-dependent sympathetic neurons that project to the eye. I determined that pruning of these projections in vivo requires the p75 neurotrophin receptor (p75NTR) and synthesis of brain-derived neurotrophic factor (BDNF) from the activity-dependent exon IV promoter. Furthermore, analysis of an in vitro model of axon competition, which is regulated by the interplay between nerve growth factor (NGF) and neuronal activity, revealed that p75NTR and BDNF are also essential for axon competition in culture. In this model, in the presence of NGF, neural activity confers a competitive growth advantage to stimulated, active axons by enhancing downstream TrkA (NGF receptor) signaling locally in axons. More interestingly, the unstimulated, inactive axons deriving from the same and neighboring neurons acquire a "growth disadvantage" due to secreted BDNF acting through p75NTR, which induces axon degeneration by suppressing TrkA signaling that is essential for axonal integrity. These data support a model where, during developmental axon competition, successful axons secrete BDNF in an activity-dependent fashion which activates p75NTR on unsuccessful neighboring axons, suppressing TrkA signaling, and ultimately promoting pruning by a degenerative mechanism.
Author: Karun K. Singh Publisher: ISBN: 9780494579275 Category : Languages : en Pages : 382
Book Description
The formation of neural connections in the mammalian nervous system is a complex process. During development, axons are initially overproduced and compete for limited quantities of target-derived growth factors. Axons which participate in functional circuits and secure appropriate amounts of growth factors are stabilized, while those axons that are either inappropriately connected or do not obtain sufficient concentrations of growth factors are eliminated in a process termed 'axon pruning'. In this thesis, I examined the mechanisms that regulate pruning of peripheral, NGF-dependent sympathetic neurons that project to the eye. I determined that pruning of these projections in vivo requires the p75 neurotrophin receptor (p75NTR) and synthesis of brain-derived neurotrophic factor (BDNF) from the activity-dependent exon IV promoter. Furthermore, analysis of an in vitro model of axon competition, which is regulated by the interplay between nerve growth factor (NGF) and neuronal activity, revealed that p75NTR and BDNF are also essential for axon competition in culture. In this model, in the presence of NGF, neural activity confers a competitive growth advantage to stimulated, active axons by enhancing downstream TrkA (NGF receptor) signaling locally in axons. More interestingly, the unstimulated, inactive axons deriving from the same and neighboring neurons acquire a "growth disadvantage" due to secreted BDNF acting through p75NTR, which induces axon degeneration by suppressing TrkA signaling that is essential for axonal integrity. These data support a model where, during developmental axon competition, successful axons secrete BDNF in an activity-dependent fashion which activates p75NTR on unsuccessful neighboring axons, suppressing TrkA signaling, and ultimately promoting pruning by a degenerative mechanism.
Author: James A. Radosevich Publisher: John Wiley & Sons ISBN: 1119432359 Category : Science Languages : en Pages : 768
Book Description
These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death. Covers all known processes that dying cells undergo Provides extensive coverage of a topic not fully covered before Offers chapters written by top researchers in the field Provides activities that link and contrast processes to each other Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.
Author: Julie Dzung Luu Publisher: ISBN: 9781339259222 Category : Languages : en Pages :
Book Description
Understanding of how neural circuits process information from the environment, produce a percept of the external stimuli, and then evoke a behavioral response has been an ultimate goal in neuroscience. To achieve this long-standing goal, we must first understand how neural circuits are established. The functionality of a mature sensory system is highly dependent on the proper formation of precise neuronal connections that convey information about environmental stimuli to specific regions of the central nervous system. The formation of neural circuitry in the developing animal occurs in a series of regulated steps. Developing neuronal precursors first undergo a series of progressive events such as cell division, cell differentiation, cell migration, neuronal extension via elongation of their axon branches, axon guidance, and establishment of synapses. During these progressive events, neurons extend an exuberant number of axons and form an excess of broad connections. The developing nervous system will subsequently undergo a series of regressive events such as cell death, synapse elimination, and pruning of axons. These regressive events refine the immature broadly patterned neural connectivity into a mature precise neural network. Perturbations of axon pruning may result in abnormal neuronal connections, which in turn can lead to deleterious behavioral effects associated with several neuropsychological disorders. The focus of my dissertation research is on the study of regulatory mechanisms underlying axon pruning during the formation of neural circuitry in the mammalian central nervous system, specifically layer 5 pyramidal corticopontine and corticospinal neurons in the visual cortex (V1). I extensively investigate the development of V1 layer 5 pyramidal neurons because both small-scale pruning of visual corticopontine terminal zone (TZ) axons and large-scale stereotyped axon pruning of visual corticospinal tract (CST) axons occur within the same cells. Surprisingly, the precise timing of development and refinement of corticopontine and corticospinal projections of V1 layer 5 pyramidal neurons are not characterized, the mechanisms for small-scale pruning of visual corticopontine TZ axons are completely unknown, and the mechanisms for large-scale stereotyped pruning of visual CST axons are incompletely determined. For my dissertation research, I investigate the development and refinement of corticopontine and corticospinal projections from V1 layer 5 pyramidal neurons. Specifically in Chapter 2, I investigate whether both small-scale pruning of visual corticopontine TZ and large-scale pruning of visual CST axons are regulated by the same set of molecular and neural activity mechanisms or differentially regulated. I will show that both small- and large-scale stereotyped pruning of V1 efferent axons are simultaneously and coordinately regulated by the same set of mechanisms: 1) Semaphorin-3F (Sema3F) signaling through Neuropilin-2 (NPN2), Plexin-A3 (PLA3), and Plexin-A4 (PLA4) co-receptors, and 2) spontaneous retinal waves, not extrinsic visually-evoked activity. By using mouse genetics and comparative approaches, I will also present several lines of evidence to demonstrate that it is the initiation of Stage 3 spontaneous retinal waves, rather than the entire duration, that is necessary for both small-scale visual corticopontine terminal axon pruning and large-scale stereotyped visual CST pruning. In Chapter 3, I investigate the development of corticospinal projections from V1 layer 5 pyramidal neurons into the spinal cord and determine whether visual CST axons descend in multiple spinal cord locations. I will demonstrate that visual CST axons initially extend into both dorsal contralateral and ventral ipsilateral spinal cord and that subsequent large-scale stereotyped pruning will eliminate visual CST axons from both spinal cord locations. I will show that subsequent large-scale stereotyped pruning of dorsal contralateral visual CST axons is regulated by both Sema3F signaling and spontaneous retinal waves interacting along the same pathway, whereas large-scale stereotyped pruning of ventral ipsilateral visual CST axons is regulated by spontaneous retinal waves but not Sema3F signaling.Thus overall, my research has elucidated molecular and neural activity mechanisms regulating axon pruning of layer 5 V1 efferent neurons to advance understanding of regulatory mechanisms underlying axon pruning during the formation of neural circuitry in the mammalian central nervous system.
Author: Stephen G. Waxman Publisher: ISBN: 0195082931 Category : Axons Languages : en Pages : 710
Book Description
The axon, interposed between the cell body and the synaptic terminals in most neurons, plays a crucial role in connecting neurons and acting as a conduit for the transmission of information between them. This book provides a comprehensive and up-to-date compendium that brings together chapterson the structure, function, and pathophysiology of axons in both the PNS and CNS. Carefully written, well-illustrated with superb illustrations, and generously referenced, the 33 chapters and introduction have been authored by 49 world-renowned authorities. Recent advances in the molecularneurobiology of axons are carefully reviewed, and new areas, such as the molecular biology of ion channels and myelination, the role of calcium in pathophysiology and regeneration, cell adhesion molecules and their roles in axo-glial interactions and axonal guidance, and optical recording methods,are highlighted. This book will provide an essential reference for neuroscientists as well as clinicians such as neurologists, neurosurgeons, and clinical electrophysiologists interested in axons.
Author: Gregory S. Walsh Publisher: ISBN: Category : Languages : en Pages : 332
Book Description
"Developmental sympathetic neuron death is determined by functional interactions between the TrkA/NGF receptor and the p75 neurotrophin receptor (p75NTR). A key question is whether p75NTR promotes apoptosis by directly inhibiting or modulating TrkA activity, or by stimulating cell death independently of TrkA. Here we show that the presence or absence of p75NTR does not alter Trk activity or NGF- and NT-3-mediated downstream survival signaling in primary neurons. Crosses of p75NTR-/- and TrkA-/-mice indicate that the coincident absence of p75NTR substantially rescues TrkA-/-sympathetic neurons from developmental death in vivo. These data support a model where developing sympathetic neurons are "destined to die" by an ongoing p75NTR-mediated apoptotic signal, and one of the major ways that TrkA promotes neuronal survival is by silencing this ongoing death signal. We then examined a role for JNK-p53 apoptotic pathway in NGF-deprived neurons and in nerve injury-induced death. Specifically, inhibition of JNK by overexpression of JIP-1 was sufficient to rescue sympathetic neurons from NGF withdrawal-induced death. In addition, JNK is robustly activated in nerve-injured neonatal facial motoneurons and these neurons are rescued from nerve-injury-induced cell death in p53 null mice. We then investigated the intracellular mechanisms that underlie the relative invulnerability of adult versus developing DRG sensory neurons. In both adult and neonatal neurons, death stimuli induced the apoptotic JNK pathway, but JNK activation only caused death of neonatal neurons, indicating that adult neurons have a downstream block to apoptosis. An essential component of this "block" is the p53 family member, DeltaNp73. Cultured adult p73+/- DRG neurons were more vulnerable to apoptotic stimuli than their p73+/+ counterparts, and invulnerability could be restored to the p73+/- neurons by increased expression of DeltaNp73. Moreover, although DRG neuron development was" --
Author: Elisabetta Babetto Publisher: Humana ISBN: 9781071605844 Category : Science Languages : en Pages : 0
Book Description
This book is a collection of classical as well as innovative methods used to investigate axon degeneration with a particular focus on addressing the common challenges encountered while performing these procedures. Particular attention is devoted to the study of axon loss in several model organisms, as each poses unique challenges and provides powerful advantages. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Axon Degeneration: Methods and Protocols is an ideal guide for facilitating the application and further development of these protocols, which will help the scientific community tackle important questions regarding axon degeneration. Chapters 2, 3, and 20 are available Open Access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Author: National Academy of Sciences Publisher: National Academies Press ISBN: 0309045290 Category : Medical Languages : en Pages : 195
Book Description
The brain ... There is no other part of the human anatomy that is so intriguing. How does it develop and function and why does it sometimes, tragically, degenerate? The answers are complex. In Discovering the Brain, science writer Sandra Ackerman cuts through the complexity to bring this vital topic to the public. The 1990s were declared the "Decade of the Brain" by former President Bush, and the neuroscience community responded with a host of new investigations and conferences. Discovering the Brain is based on the Institute of Medicine conference, Decade of the Brain: Frontiers in Neuroscience and Brain Research. Discovering the Brain is a "field guide" to the brainâ€"an easy-to-read discussion of the brain's physical structure and where functions such as language and music appreciation lie. Ackerman examines: How electrical and chemical signals are conveyed in the brain. The mechanisms by which we see, hear, think, and pay attentionâ€"and how a "gut feeling" actually originates in the brain. Learning and memory retention, including parallels to computer memory and what they might tell us about our own mental capacity. Development of the brain throughout the life span, with a look at the aging brain. Ackerman provides an enlightening chapter on the connection between the brain's physical condition and various mental disorders and notes what progress can realistically be made toward the prevention and treatment of stroke and other ailments. Finally, she explores the potential for major advances during the "Decade of the Brain," with a look at medical imaging techniquesâ€"what various technologies can and cannot tell usâ€"and how the public and private sectors can contribute to continued advances in neuroscience. This highly readable volume will provide the public and policymakersâ€"and many scientists as wellâ€"with a helpful guide to understanding the many discoveries that are sure to be announced throughout the "Decade of the Brain."
Author: Karun K. Singh
Author: Karun K. Singh
Author: Karun Singh
Author: Ryan Jefferson Watts
Author: James A. Radosevich
Author: Julie Dzung Luu
Author: Stephen G. Waxman
Author: Gregory S. Walsh
Author: Elisabetta Babetto
Author: National Academy of Sciences
Author: Nadia Sophia Khalid Haque