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Dynamics of Degeneration and Growth in Neurons is a collection of papers presented at the International Symposium on the Dynamics of Degeneration and Growth in Neurons, held in Stockholm, Sweden, on May 16-18, 1973. Contributors explore the dynamics of degeneration and growth of central and peripheral neurons, touching on a wide range of topics such as the neurotoxic action of 6-hydroxy-dopa on central catecholamine neurons; axonal transport of proteins in growing and regenerating neurons; and collateral reinnervation in the central nervous system. Comprised of 50 chapters, this volume begins with an overview of degeneration processes in central and peripheral neurons. Results of microfluorimetric and neurochemical studies on degenerating and regenerating adrenergic nerves are presented. The next section is devoted to axoplasmic transport as a mechanism for axonal support and growth and includes chapters dealing with the effects of degeneration and axoplasmic transport blockade on synaptic ultrastructure, function, and protein composition; the role of axoplasmic flow in trophism of skeletal muscle; and proximodistal transport of acetylcholine in peripheral cholinergic neurons. The remaining chapters discuss the nerve growth factor receptor and its specific binding in sympathetic ganglia; the noradrenergic innervation of cerebellar Purkinje cells; and the possible role of brain and peripheral monoamines in the ontogenesis of normal and drug-induced responses in the immature mammal. This book will be of interest to physiologists and neurologists.
Degeneration and Regeneration in the Nervous System brings together an international team of contributors to produce a series of critical reviews appraising key papers in the field. The pace of research on brain and spinal cord injury quickened considerably in the last ten years and there is much that is new and important that is covered in this bo
This book is the result of the 20th International Summer School in Brain Research, organized in August 1997 in Amsterdam, by the Netherlands Institute for Brain Research at the Royal Netherlands Academy of Sciences. It is the first book that provides a complete overview of the field of neurodegeneration and regeneration including spinal cord injury, neurodegenerative diseases and therapy. Divided into five sections, the first two sections give an overview of fundamental research on nerve cell death, neuronal survival, neurite outgrowth and guidance. Extensive attention is given to the role of neurotrophins, their receptor tyrosine kinases and cell-adhesion molecules in development and regeneration of the nervous system. The third section of the book is devoted to research involving human neurodegenerative diseases and emerging treatment strategies. Section four focusses on recent advances in the understanding of pathophysiological mechanisms underlying neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases along with prion diseases. Novel insights into the neuropathological hallmarks of these diseases, as well as into transgenic animal models, the involvement of environmental factors, and genomic and mRNA changes that can cause neurodegeneration. The final section of this volume reveals recent developments in the use of cell and gene therapy to treat neurodegenerative disease and lesion-related deficits. Implantation of genetically modified cells, direct gene transfer with viral vectors and the first clinical trials with encapsulated genetically modified cells in patients suffering from amyotrophic lateral scelerosis are examples of new therapeutic strategies treating neurodegenerative diseases. The book is of particular interest to departments of neuroscience, neurological clinics and departments, the pharmalogical industry and medical libraries.
This book examines recent key findings on the mechanisms of axonal and dendritic remodeling in different model organisms. Each chapter is contributed by a panel of experts in their respective subfields of neurosciences, to provide and discuss the latest discoveries ranging from neuronal morphogenesis during development, experience-dependent structural plasticity, to neuronal degeneration, regeneration, and pathologies in neurological disorders. The process of neuronal remodeling, specifically their axons and dendrites, is essential for the proper wiring of the nervous system during early development and continues during postnatal ages to shape the pattern of synaptic connections throughout the life of the organism, including humans. Over recent years, substantial progress has been made in our understanding of the cellular and molecular mechanisms that control neuronal remodeling. In addition, there is accumulating evidence demonstrating how the nervous system could remodel in response to injury and in pathological conditions. Topics discussed in the book include: Axonal degeneration during development and in pathological or disease conditions Neuronal morphogenesis (axons and dendrites) Experience-dependent structural plasticity to synaptogenesis Dendrite degeneration and regeneration
Ever since Santiago Ramón y Cajal sketched his captivating panels of the microscopic structure of the brain with its vast diversity of neuronal morphology over a century ago, scientists have been drawn to this seemingly chaotic network of neurites and processes to uncover how structure relates to function. During the course of a century, we have moved from merely describing neuronal and glial morphology to furthering our understanding of such intricate processes as organelle and factor transport, cellular compartmentalization, neuronal polarity, cytoskeleton dynamics, neurite pathfinding, and the impact of pathophysiological insult on these structures and events. Yet to this day, and likely for the foreseeable future, much work remains to be done to fully grasp the exceptional role of neurites for the function of larger neuronal ensembles and networks. While the somatodendritic domain of neurons has been in the focus of attention for many years, mostly because of its great dynamic remodeling capacity during events of plasticity (e.g. learning), the axonal domain has somehow remained in the background despite the fact that especially recent comprehensive studies from various fields of research underline the axon’s contribution to dynamic plasticity processes. Consequently, this Research Topic focuses on the many exciting aspects of axonal neurobiology – ranging from membrane composition and molecular determination during development to axonal domain specialization and physiology in health and disease. In Chapter 1 “Axons in the PNS”, Bombeiro et al. use immunodeficient mice to study the role of lymphocytes during the regeneration of peripheral nerves, showing that the modulation of immune responses after injury can be an efficient approach to enhance nerve regeneration in the PNS. Using a DRG model, Berbusse et al. identify the onset of damage to mitochondrial structure and dynamics as a key event during early axon degeneration and provide evidence that Nmnat1, a member of the family of nicotinamide-nucleotide adenylyltransferases, can have protective effects by preserving normal mitochondrial integrity and dynamics. In another study of PNS nerve regeneration, Law et al. use proteomics approaches via Mass Spectrometry to provide evidence that rosovitine, a synthetic purine nucleoside analog, can successfully promote PNS axon regeneration. In Chapter 2 “Axonal development in the central nervous system”, Yoshimura et al. analyze specialized axonal domains, namely the axon initial segment and nodes of Ranvier, with regards to their expression profiles of the major scaffolding protein ßIV-spectrin. Super resolution microscopy reveals a potential developmental switch of spectrin isoforms at both axonal domains. In a related study, also using super resolution microscopy, Leterrier et al. examine a potential reciprocal role of membrane partners in ankyrin-G targeting and stabilization at the axonal membrane during development. The authors demonstrate a tight and precocious association of ankyrin-G with its membrane partners. Höfflin et al. address the question of axon initial segment morphology across different cell classes in cortical organotypic slice cultures and find a surprising heterogeneity especially between pyramidal cells and interneurons in primary visual cortex. In a major step towards establishing a successful live label of the axon initial segment, Dumitrescu et al. report the development of a genetically-encoded construct consisting of a voltage-gated sodium channel intracellular domain fused to yellow fluorescent protein (YFP-NaVII-III). Nelson and Jenkins then provide a comprehensive Review article on the axon initial segment and nodes of Ranvier with a special focus on the various scaffolding protein isoforms and their role in human disease. In Chapter 3 “Axonal physiology and plasticity”, Nikitin et al. investigate fast onset dynamics of action potentials during neuronal development in vitro, showing that encoding of high frequencies improves upon culture maturation, accompanied by the development of passive electrophysiological properties and action potential generation. Using pharmacological and RNA interference approaches, Tapia et al. provide evidence that cannabinoid receptors and their ligands can modulate dendritic morphology and thus, indirectly, also affect ankyrin-G accumulation at the axon initial segment. A Mini Review by Zbili et al. discusses the potential impact of subthreshold changes in presynaptic membrane potential before action potential initiation on neurotransmitter release, and which significant impact such mechanisms could have on information processing in neuronal circuits. Yamada and Kuba close this chapter with a Mini Review on axon initial segment plasticity with a particular focus on ion channels and the biophysics of excitability. In Chapter 4 “Axon degeneration and regeneration”, Hamada et al. investigate the often overlooked question to which extent myelin loss affects action potential propagation along distal branch points and axon collaterals. Using the cuprizone demyelination model and optical voltage-sensitive dye imaging, the authors uncover functional consequences of demyelination that reach well beyond the main axon. In a model of mild traumatic brain injury, Vascak et al. demonstrate complex aspects of this injury type on neocortical circuit function, including changes in inhibitory perisomatic input and axon initial segment-driven output in affected layer V neurons. In a Mini Review, Grosch et al. discuss recent advances in the field of Parkinson’s disease with a focus on early degeneration in dopaminergic and serotonergic neurons of the basal ganglia. The last two articles cover the topic of axonal regeneration. Li et al. investigate the role of activated astrocytes in spinal cord lesion and how their functional downregulation via an inhibitor of mitochondrial fission, Mdivi-1, could potentially have positive impact on lesion scar formation and axonal regeneration. In a final Review, Liu et al. highlight recent advances in the development of biomaterial scaffolds and cell transplantation strategies to combine two promising therapeutic approaches for spinal cord injury.
Spinal cord injury is a permanent, physically, and occasionally mentally, debilitating condition with no robust panacea available. Currently, there are 5.6 million Americans living with spinal cord injury, with and estimate of 10,000-12,000 new injuries per year [1]. The permanency of the functional deficits after spinal cord injury is due to the inability of central nervous system (CNS) axons to regenerate, which in turn is attributed to a multitude of neuron-intrinsic and extrinsic factors. Studies of spinal cord injury have traditionally been hampered by the difficulty of identifying regenerating axons, a myriad of confounding variables, and limited temporal and spatial resolution. The main goal of my thesis work is to develop in vivo imaging with 2-photon microscopy to study spinal axon responses to injury in living mice, and to start to apply this experimental paradigm to the studies of axon growth regulators. I have found that in vivo imaging is a powerful tool to investigate the dynamic responses of spinal axons to axonal injury. In Chapter 2, the main and publication-ready part of my thesis, I describe the baseline axonal dynamics, including degeneration and regeneration, after laser-mediated axotomy in the mouse spinal cord. The data depict the detailed behaviors of single sensory axons over hours (acute), days (sub-acute), weeks (sub-chronic), and months (chronic). An earlier phase of axon degeneration is followed by later phases of axonal regeneration, pruning and remodeling up to 6 months after the initial axotomy. Branch points and nodes of Ranvier emerge as important determinants of axonal degeneration and regeneration following injury. It will be difficult, if not impossible, to gain such insights from conventional models of spinal cord injury. In Chapter 3, I describe efforts to apply this imaging paradigm to examine the effects of deleting the prototypical myelin associated axon growth inhibitor, Nogo. I found that Nogo deletion slows the acute degenerative process, and also (regeneration results coming). Chapter 4 describes my collaborative effort with another lab member to examine the effect of combined deletion of Nogo and PTEN, a neuron-intrinsic inhibitor of regeneration. The results provide proof of principle evidence that manipulating both intrinsic and extrinsic growth regulators may lead to further enhancement in axonal growth after injury. My involvement in this project was meant to complement my imaging studies, which used a minimal laser injury model. In Chapter 5, I provide perspective for future endeavors.