Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research. This volume reviews existing theories and current research surrounding Axon Growth and Regeneration. - Leading authors review state-of-the-art in their field of investigation and provide their views and perspectives for future research - Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered - All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist

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 book. However, there is still a long way to go before our knowledge will explain fully why the central nervous system has such a limited capacity for regeneration, and before experimental solutions can be applied to the patient. With emphasis on actual and therapeutic importance of the work reviewed, Degeneration and Regeneration in the Nervous System is a useful overview for graduate students, their teachers and researchers working in this field.

Leading authors review state-of-the-art in their field of investigation and provide their views and perspectives for future research. Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered. All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist - Leading authors review state-of-the-art in their field of investigation and provide their views and perspectives for future research - Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered - All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist

Axonal connectivity is established by regulated guidance of growing axons during development and maintained by proper neuronal responses to damage in adult organisms. This study investigates different aspects of axonal biology that are required for integrity of axons: axon guidance, axon regeneration, and axon degeneration. During development, axons often form synapses with multiple targets by extending branches along different paths. We demonstrate that Highwire, the Drosophila member of PHR family ubiquitin ligases, is required for the segregation of sister axons in the developing Drosophila brain. Loss of highwire leads to thinning and shortening of the axonal lobes in the mushroom body, due to guidance errors following axon branching. We show that elevation in the level of the MAPKKK dual leucine zipper kinase (DLK), a previously identified substrate of Highwire, is responsible for the highwire phenotype. Genetic studies demonstrate a non cell-autonomous role of Highwire and also suggest that Plexin A signals may interact with Highwire to regulate axonal guidance. We next study how axons react to injury to restore neural function. When axons are severed by injury, distal axons degenerate whereas proximal axon stumps sometimes regenerate and re-build the functional connectivity. We show that DLK promotes injury-induced regeneration (pre-conditioning effect) of axons following peripheral nerve injury in mice. DLK is required for retrograde transport of axon injury signaling components to the cell body and promotes upregulation of pro-regenerative transcription factors. These data demonstrate that DLK regulates early responses to injury that subsequently reprogram a neuron to better regenerate. Axon degeneration is a consequence of a variety of neurological disorders as well as traumatic injury. The c-Jun N-terminal kinase (JNK) pathway is required for axonal destruction shortly after axonal injury. We identify superior cervical ganglion 10 (SCG10) as an axonal JNK substrate during axon degeneration. SCG10 undergoes fast turnover and replenishment by axon transport in healthy axons. Following axotomy SCG10 is rapidly lost from distal axons due to the lack of supply from the cell body. SCG10 degradation requires JNK activity in both injured and uninjured axons. We show that SCG10 loss is functionally important because preservation of SCG10 is sufficient to delay axon fragmentation.

Axon Growth and Regeneration: Methods and Protocols brings together a diverse set of techniques for the study of the mechanisms underlying central nervous system axon growth, consequently providing a resource that will aid in the development of repair strategies. After an introductory section, this detailed volume continues with sections focusing on axon growth in vitro, providing a range of protocols that can be used to examine intracellular signalling pathways, axonal responses to extracellular factors and methods for quantifying outgrowth. The next section provides protocols for inducing experimental injury in vivo as well as some highly promising protocols for promoting regeneration, which segues into the final section highlighting a series of protocols that can be used to monitor the extent of axon regeneration in vivo, ranging from tract tracing to in vivo imaging and functional recovery. As a book in the Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and tips on troubleshooting and avoiding known pitfalls. Practical and reliable, Axon Growth and Regeneration: Methods and Protocols aims to serve researchers studying axon regeneration with a significant set of diverse tools, vital for moving on to the next generation of exciting new discoveries in the field.

Debilitating neurodegeneration due to brain injury or disease currently has limited treatment options and no cures. Endogenous repair mechanisms could provide targets for novel regenerative therapies. Drosophila melanogaster is a leading model for studies of neural development; however, this model has not been exploited to investigate the capacity of regeneration in the adult brain. This is primarily due to earlier studies demonstrating that adult Drosophila brains have limited mitotic activity and that neural progenitors undergo apoptosis during metamorphosis. We have developed and used a novel model of neural injury termed penetrating traumatic brain injury (PTBI) to investigate the capacity of neuroregeneration in adult central brains. Within 24 hours after injury, we observe a robust proliferative response and upregulation of neural progenitor genes. While there is some cell death post-PTBI, this is limited to early timepoints after injury; by 10 days, the amount of cell death is not significantly different from non-injured age-matched controls. Cell division continues out to 14 days post- injury, with the creation of new neurons and new glia. Using cell lineage-tracing techniques, we found that new neurons are generated by cells that had once expressed dpn; these dpn-expressing cells are not found in uninjured controls. Taken together, our data support the idea that there is a quiescent NB-like population of cells that is activated upon injury, specifically in young adult flies. The newly created cells are able to contribute to the overall regeneration of damaged brain tissue, particularly near the mushroom body. Indeed, while flies 2 days post-PTBI have locomotor defects and significantly different sleep profiles compared to uninjured controls, by 14 days post- PTBI, locomotor activity and sleep is restored back to normal levels. We find that other factors, including socialization and light, impact the ability of flies to recover and warrant further investigation. We anticipate that our model will allow us to further dissect the mechanisms by which this occurs and anticipate that these processes will have relevance to mammals, including humans.

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.