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Experimental Neurology May 2010Regeneration in the peripheral nervous system offers unique opportunities and challenges to medicine. Compared to the central nervous system, peripheral axons can and do...
Regeneration in the peripheral nervous system offers unique opportunities and challenges to medicine. Compared to the central nervous system, peripheral axons can and do regenerate resulting in functional recovery, especially if the distance to target is short as in distal limb injuries. However, this regenerative capacity is often incomplete and functional recovery with proximal lesions is limited. Furthermore, regeneration of axons to the appropriate targets remains a challenge with inappropriate reinnervation being an impediment to full recovery. The reviews and selected original research papers in this Special Issue will address some of these challenges and highlight new opportunities for development of effective therapies for nerve regeneration.
Topics: Animals; Axons; Humans; Nerve Regeneration; Peripheral Nervous System; Recovery of Function
PubMed: 20004660
DOI: 10.1016/j.expneurol.2009.12.001 -
Stem Cells Translational Medicine Aug 2013Repair in the peripheral nervous system (PNS) depends upon the plasticity of the myelinating cells, Schwann cells, and their ability to dedifferentiate, direct axonal... (Review)
Review
Repair in the peripheral nervous system (PNS) depends upon the plasticity of the myelinating cells, Schwann cells, and their ability to dedifferentiate, direct axonal regrowth, remyelinate, and allow functional recovery. The ability of such an exquisitely specialized myelinating cell to revert to an immature dedifferentiated cell that can direct repair is remarkable, making Schwann cells one of the very few regenerative cell types in our bodies. However, the idea that the PNS always repairs after injury, in contrast to the central nervous system, is not true. Repair in patients after nerve trauma can be incredibly variable, depending on the site and type of injury, and only a relatively small number of axons may fully regrow and reinnervate their targets. Recent research has shown that it is an active process that drives Schwann cells back to an immature state after injury and that this requires activity of the p38 and extracellular-regulated kinase 1/2 mitogen-activated protein kinases, as well as the transcription factor cJun. Analysis of the events after peripheral nerve transection has shown how signaling from nerve fibroblasts forms Schwann cells into cords in the newly generated nerve bridge, via Sox2 induction, to allow the regenerating axons to cross the gap. Understanding these pathways and identifying additional mechanisms involved in these processes raises the possibility of both boosting repair after PNS trauma and even, possibly, blocking the inappropriate demyelination seen in some disorders of the peripheral nervous system.
Topics: Animals; Humans; MAP Kinase Signaling System; Myelin Sheath; Neuronal Plasticity; Peripheral Nervous System; Schwann Cells; Wound Healing
PubMed: 23817134
DOI: 10.5966/sctm.2013-0011 -
Cells Jul 2020The peripheral nervous system has retained through evolution the capacity to repair and regenerate after assault from a variety of physical, chemical, or biological... (Review)
Review
The peripheral nervous system has retained through evolution the capacity to repair and regenerate after assault from a variety of physical, chemical, or biological pathogens. Regeneration relies on the intrinsic abilities of peripheral neurons and on a permissive environment, and it is driven by an intense interplay among neurons, the glia, muscles, the basal lamina, and the immune system. Indeed, extrinsic signals from the milieu of the injury site superimpose on genetic and epigenetic mechanisms to modulate cell intrinsic programs. Here, we will review the main intrinsic and extrinsic mechanisms allowing severed peripheral axons to re-grow, and discuss some alarm mediators and pro-regenerative molecules and pathways involved in the process, highlighting the role of Schwann cells as central hubs coordinating multiple signals. A particular focus will be provided on regeneration at the neuromuscular junction, an ideal model system whose manipulation can contribute to the identification of crucial mediators of nerve re-growth. A brief overview on regeneration at sensory terminals is also included.
Topics: Humans; Nerve Regeneration; Neurons; Peripheral Nervous System; Schwann Cells
PubMed: 32722089
DOI: 10.3390/cells9081768 -
Frontiers in Immunology 2021The peripheral nervous system consists of sensory circuits that respond to external and internal stimuli and effector circuits that adapt physiologic functions to... (Review)
Review
The peripheral nervous system consists of sensory circuits that respond to external and internal stimuli and effector circuits that adapt physiologic functions to environmental challenges. Identifying neurotransmitters and neuropeptides and the corresponding receptors on immune cells implies an essential role for the nervous system in regulating immune reactions. Vice versa, neurons express functional cytokine receptors to respond to inflammatory signals directly. Recent advances in single-cell and single-nuclei sequencing have provided an unprecedented depth in neuronal analysis and allowed to refine the classification of distinct neuronal subsets of the peripheral nervous system. Delineating the sensory and immunoregulatory capacity of different neuronal subsets could inform a better understanding of the response happening in tissues that coordinate physiologic functions, tissue homeostasis and immunity. Here, we summarize current subsets of peripheral neurons and discuss neuronal regulation of immune responses, focusing on neuro-immune interactions in the gastrointestinal tract. The nervous system as a central coordinator of immune reactions and tissue homeostasis may predispose for novel promising therapeutic approaches for a large variety of diseases including but not limited to chronic inflammation.
Topics: Animals; Biomarkers; Disease Susceptibility; Gene Expression Regulation; Humans; Immunomodulation; Neuroimmunomodulation; Neurons; Peripheral Nervous System; Signal Transduction
PubMed: 34322118
DOI: 10.3389/fimmu.2021.679055 -
Glia Dec 2022Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in... (Review)
Review
Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate after injury. SCs derive from the neural crest, are highly dependent on extrinsic signals, and have plastic differentiation states. SC precursors (SCPs) are produced in early embryonic nerve structures and differentiate into multipotent immature SCs (iSCs), which initiate radial sorting and differentiate into myelinating and non-myelinating SCs. Differentiated SCs retain the capacity to radically change phenotypes in response to external signals, including becoming repair SCs, which drive peripheral regeneration. While several transcription factors and myelin components are common between OLs and SCs, their differentiation mechanisms are highly distinct, owing to their unique lineages and their respective environments. In addition, both OLs and SCs respond to neuronal activity and regulate nervous system output in reciprocal manners, possibly through different pathways. Here, we outline their basic developmental programs, mechanisms regulating their differentiation, and recent advances in the field.
Topics: Female; Humans; Myelin Sheath; Neuroglia; Peripheral Nervous System; Pregnancy; Schwann Cells; Transcription Factors
PubMed: 35785432
DOI: 10.1002/glia.24238 -
International Journal of Molecular... Apr 2023It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development... (Review)
Review
It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice versa is constantly increasing and several 'gut-organ axes' have already been defined. Recently, the view on the link between the gut microbiota (GM) and the peripheral nervous system (PNS) has become broader by exceeding the fact that the PNS can serve as a systemic carrier of GM-derived metabolites and products to other organs. The PNS as the communication network between the central nervous system and the periphery of the body and internal organs can rather be affected itself by GM perturbation. In this review, we summarize the current knowledge about the impact of gut microbiota on the PNS, with regard to its somatic and autonomic divisions, in physiological, regenerative and pathological conditions.
Topics: Humans; Gastrointestinal Microbiome; Central Nervous System; Peripheral Nervous System
PubMed: 37175764
DOI: 10.3390/ijms24098061 -
Current Opinion in Cell Biology Dec 2019Several decades of intense research provided us with a grand framework describing the emergence of neurons in central (CNS) and peripheral (PNS) nervous systems.... (Review)
Review
Several decades of intense research provided us with a grand framework describing the emergence of neurons in central (CNS) and peripheral (PNS) nervous systems. However, the specifics of molecular events and lineage control leading to a plethora of neuronal subtypes stayed largely unclear. Today, the advances in single cell omics, sample clearing and 3D-microscopy techniques, brain organoids, and synaptic connectivity tracing enabled systematic and unbiased understanding of neuronal diversity, development, circuitry and cell identity control. Novel technological advancements stimulated the transition from conceptual scheme of neuronal differentiation into precise maps of molecular events leading to the diversity of specific neuronal subtypes in relation to their locations and microenvironment. These high-resolution data opened a set of new questions including how transcriptional and epigenetics states control the proportionality of neuronal subpopulations or what are the evolutionary mechanisms of origin of different neuronal subtypes. In this review, we outline the most recent advancements in our understanding of how the neuronal diversity is generated in CNS and PNS and briefly address the challenges and questions arising in the field of neurogenesis.
Topics: Animals; Cell Differentiation; Central Nervous System; Models, Biological; Neural Stem Cells; Neurons; Peripheral Nervous System
PubMed: 31369951
DOI: 10.1016/j.ceb.2019.07.003 -
Science (New York, N.Y.) Aug 2019The central and peripheral nervous system (CNS and PNS, respectively) are composed of distinct neuronal and glial cell types with specialized functional properties.... (Review)
Review
The central and peripheral nervous system (CNS and PNS, respectively) are composed of distinct neuronal and glial cell types with specialized functional properties. However, a small number of select cells traverse the CNS-PNS boundary and connect these two major subdivisions of the nervous system. This pattern of segregation and selective connectivity is established during embryonic development, when neurons and glia migrate to their destinations and axons project to their targets. Here, we provide an overview of the cellular and molecular mechanisms that control cell migration and axon guidance at the vertebrate CNS-PNS border. We highlight recent advances on how cell bodies and axons are instructed to either cross or respect this boundary, and present open questions concerning the development and plasticity of the CNS-PNS interface.
Topics: Animals; Astrocytes; Axon Guidance; Basement Membrane; Cell Movement; Central Nervous System; Neuroglia; Neurons; Peripheral Nervous System
PubMed: 31467195
DOI: 10.1126/science.aaw8231 -
The Journal of Investigative... Aug 1997Major advances have been made in our understanding of autonomic and sensory transmission and function during the past two decades. These include (i) the establishment of... (Review)
Review
Major advances have been made in our understanding of autonomic and sensory transmission and function during the past two decades. These include (i) the establishment of the role of sympathetic and parasympathetic ganglia in relaying neuronal information from the central nervous system to effector organs, (ii) the recognition that enteric ganglia, the third component of the autonomic nervous system, contain independent integrative circuits that control complex local activities, (iii) the evidence for local effector functions of primary sensory nerves in addition to their role in sensory transmission, and (iv) the discovery of plasticity of both autonomic and sensory neurons during disease states and inflammation. A major contribution to these new concepts has been the recognition that in both autonomic and sensory ganglia a variety of transmitters coexist in single neurons. Co-transmission is a widespread phenomenon that enables autonomic and sensory neurons to exert fine and highly regulated control of various functions such as circulation, respiration, digestion, and immune response. This chapter will focus on the general principles and specific features of autonomic and sensory ganglia, with a particular emphasis on their general organization and neurochemical properties. Classical concepts and modern principles of classification of autonomic and sensory ganglia are discussed.
Topics: Animals; Autonomic Nervous System; Axons; Ganglia, Autonomic; Ganglia, Sensory; Humans; Neurons; Neurons, Afferent; Peripheral Nervous System
PubMed: 9487007
DOI: 10.1038/jidsymp.1997.2 -
Developmental Biology Feb 2015During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to... (Review)
Review
During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord. The emergence of molecular cloning techniques and identification of fluorophores like Green Fluorescent Protein (GFP), together with transgenic and electroporation technologies, have made it possible to easily visualize the cellular and molecular events in play during nervous system formation. These lineage-tracing techniques have precisely demonstrated the migratory pathways followed by neural crest cells and increased knowledge about their differentiation into PNS derivatives. Similarly, in the spinal cord, lineage-tracing techniques have led to a greater understanding of the regional organization of multiple classes of neural progenitor and post-mitotic neurons along the different axes of the spinal cord and how these distinct classes of neurons assemble into the specific neural circuits required to realize their various functions. Here, we review how both classical and modern lineage and marker analyses have expanded our knowledge of early peripheral nervous system and spinal cord development.
Topics: Animals; Axons; Cell Lineage; Cell Movement; Humans; Peripheral Nervous System; Spinal Cord; Torso
PubMed: 25446276
DOI: 10.1016/j.ydbio.2014.09.033