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Nature Communications May 2022Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor...
Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found in NF1 patients lacking neurofibromas or optic gliomas, do not exhibit neuronal hyperexcitability or develop these NF1-associated tumors. The hyperexcitability of tumor-prone Nf1-mutant neurons results from reduced NF1-regulated hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function, such that neuronal excitability, activity-regulated paracrine factor production, and tumor progression are attenuated by HCN channel activation. Collectively, these findings reveal that NF1 mutations act at the level of neurons to modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production.
Topics: Animals; Humans; Mice; Neurofibroma; Neurofibromatosis 1; Neurofibromin 1; Neurons; Optic Nerve Glioma; Peripheral Nervous System; Schwann Cells
PubMed: 35589737
DOI: 10.1038/s41467-022-30466-6 -
Neurobiology of Disease Jan 2023The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure... (Review)
Review
The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure neuronal survival and participate in axonal path finding. Simultaneously, they orchestrate the architectural set up of the developing nerves, including the blood vessels and the endo-, peri- and epineurial layers. Perinatally, in rodents, SCs radially sort and subsequently myelinate individual axons larger than 1 μm in diameter, while small calibre axons become organised in non-myelinating Remak bundles. SCs have a vital role in maintaining axonal health throughout life and several specialized SC types perform essential functions at specific locations, such as terminal SC at the neuromuscular junction (NMJ) or SC within cutaneous sensory end organs. In addition, neural crest derived satellite glia maintain a tight communication with the soma of sensory, sympathetic, and parasympathetic neurons and neural crest derivatives are furthermore an indispensable part of the enteric nervous system. The remarkable plasticity of SCs becomes evident in the context of a nerve injury, where SC transdifferentiate into intriguing repair cells, which orchestrate a regenerative response that promotes nerve repair. Indeed, the multiple adaptations of SCs are captivating, but remain often ill-resolved on the molecular level. Here, we summarize and discuss the knowns and unknowns of the vast array of functions that this single cell type can cover in peripheral nervous system development, maintenance, and repair.
Topics: Humans; Schwann Cells; Peripheral Nerves; Axons; Neurons; Peripheral Nervous System; Nerve Regeneration; Peripheral Nerve Injuries
PubMed: 36493976
DOI: 10.1016/j.nbd.2022.105952 -
Biomolecules Jul 2021Cholinesterases are fundamental players in the peripheral and central nervous systems [...].
Cholinesterases are fundamental players in the peripheral and central nervous systems [...].
Topics: Acetylcholinesterase; Animals; Butyrylcholinesterase; Central Nervous System; Cholinesterase Inhibitors; GPI-Linked Proteins; Gene Expression; Humans; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Peripheral Nervous System; Synapses; Synaptic Transmission
PubMed: 34439787
DOI: 10.3390/biom11081121 -
Neurotherapeutics : the Journal of the... Oct 2021Myelin is a key evolutionary specialization and adaptation of vertebrates formed by the plasma membrane of glial cells, which insulate axons in the nervous system.... (Review)
Review
Myelin is a key evolutionary specialization and adaptation of vertebrates formed by the plasma membrane of glial cells, which insulate axons in the nervous system. Myelination not only allows rapid and efficient transmission of electric impulses in the axon by decreasing capacitance and increasing resistance but also influences axonal metabolism and the plasticity of neural circuits. In this review, we will focus on Schwann cells, the glial cells which form myelin in the peripheral nervous system. Here, we will describe the main extrinsic and intrinsic signals inducing Schwann cell differentiation and myelination and how myelin biogenesis is achieved. Finally, we will also discuss how the study of human disorders in which molecules and pathways relevant for myelination are altered has enormously contributed to the current knowledge on myelin biology.
Topics: Animals; Axons; Biology; Humans; Myelin Sheath; Neuroglia; Schwann Cells
PubMed: 34244924
DOI: 10.1007/s13311-021-01083-w -
Journal of Anatomy Nov 2022Recent years have seen an evolving appreciation for the role of glial cells in the nervous system. As we move away from the typical neurocentric view of neuroscience,... (Review)
Review
Recent years have seen an evolving appreciation for the role of glial cells in the nervous system. As we move away from the typical neurocentric view of neuroscience, the complexity and variability of central nervous system glia is emerging, far beyond the three main subtypes: astrocytes, oligodendrocytes, and microglia. Yet the diversity of the glia found in the peripheral nervous system remains rarely discussed. In this review, we discuss the developmental origin, morphology, and function of the different populations of glia found in the peripheral nervous system, including: myelinating Schwann cells, Remak Schwann cells, repair Schwann cells, satellite glia, boundary cap-derived glia, perineurial glia, terminal Schwann cells, glia found in the skin, olfactory ensheathing cells, and enteric glia. The morphological and functional heterogeneity of glia found in the periphery reflects the diverse roles the nervous system performs throughout the body. Further, it highlights a complexity that should be appreciated and considered when it comes to a complete understanding of the peripheral nervous system in health and disease.
Topics: Astrocytes; Central Nervous System; Neuroglia; Peripheral Nerves; Schwann Cells
PubMed: 34131911
DOI: 10.1111/joa.13484 -
Annual Review of Biomedical Engineering Jun 2023Neurotechnologies for treating pain rely on electrical stimulation of the central or peripheral nervous system to disrupt or block pain signaling and have been... (Review)
Review
Neurotechnologies for treating pain rely on electrical stimulation of the central or peripheral nervous system to disrupt or block pain signaling and have been commercialized to treat a variety of pain conditions. While their adoption is accelerating, neurotechnologies are still frequently viewed as a last resort, after many other treatment options have been explored. We review the pain conditions commonly treated with electrical stimulation, as well as the specific neurotechnologies used for treating those conditions. We identify barriers to adoption, including a limited understanding of mechanisms of action, inconsistent efficacy across patients, and challenges related to selectivity of stimulation and off-target side effects. We describe design improvements that have recently been implemented, as well as some cutting-edge technologies that may address the limitations of existing neurotechnologies. Addressing these challenges will accelerate adoption and change neurotechnologies from last-line to first-line treatments for people living with chronic pain.
Topics: Humans; Chronic Pain; Electric Stimulation Therapy; Pain Management; Electric Stimulation; Peripheral Nervous System
PubMed: 37068766
DOI: 10.1146/annurev-bioeng-111022-121637 -
Current Topics in Developmental Biology 2022Proper innervation of peripheral organs helps to maintain physiological homeostasis and elicit responses to external stimuli. Disruptions to normal function can result...
Proper innervation of peripheral organs helps to maintain physiological homeostasis and elicit responses to external stimuli. Disruptions to normal function can result in pathophysiological consequences. The establishment of connections and communication between the central nervous system and the peripheral organs is accomplished through the peripheral nervous system. Neuronal connections with target tissues arise from ganglia partitioned throughout the body. Organ innervation is initiated during development with stimuli being conducted through several types of neurons including sympathetic, parasympathetic, and sensory. While the physiological modulation of mature organs by these nerves is largely understood, their role in mammalian development is only beginning to be uncovered. Interactions with cells in target tissues can affect the development and eventual function of several organs, highlighting their significance. This chapter will cover the origin of peripheral neurons, factors mediating organ innervation, and the composition and function of organ-specific nerves during development. This emerging field aims to identify the functional contribution of innervation to development which will inform future investigations of normal and abnormal mammalian organogenesis, as well as contribute to regenerative and organ replacement efforts where nerve-derived signals may have significant implications for the advancement of such studies.
Topics: Animals; Central Nervous System; Mammals; Nervous System Physiological Phenomena; Neurons; Organogenesis; Peripheral Nervous System
PubMed: 35461566
DOI: 10.1016/bs.ctdb.2022.02.004 -
Neurochemistry International Oct 2019
Topics: Animals; Blood Vessels; Cerebrovascular Circulation; Humans; Nervous System; Nervous System Diseases; Neural Pathways; Peripheral Nervous System; Retinal Vessels
PubMed: 31323247
DOI: 10.1016/j.neuint.2019.104506 -
Glia Feb 2021Schwann cells within the peripheral nervous system possess a remarkable regenerative potential. Current research shows that peripheral nerve-associated Schwann cells... (Review)
Review
Schwann cells within the peripheral nervous system possess a remarkable regenerative potential. Current research shows that peripheral nerve-associated Schwann cells possess the capacity to promote repair of multiple tissues including peripheral nerve gap bridging, skin wound healing, digit tip repair as well as tooth regeneration. One of the key features of the specialized repair Schwann cells is that they become highly motile. They not only migrate into the area of damaged tissue and become a key component of regenerating tissue but also secrete signaling molecules to attract macrophages, support neuronal survival, promote axonal regrowth, activate local mesenchymal stem cells, and interact with other cell types. Currently, the importance of migratory Schwann cells in tissue regeneration is most evident in the case of a peripheral nerve transection injury. Following nerve transection, Schwann cells from both proximal and distal nerve stumps migrate into the nerve bridge and form Schwann cell cords to guide axon regeneration. The formation of Schwann cell cords in the nerve bridge is key to successful peripheral nerve repair following transection injury. In this review, we first examine nerve bridge formation and the behavior of Schwann cell migration in the nerve bridge, and then discuss how migrating Schwann cells direct regenerating axons into the distal nerve. We also review the current understanding of signals that could activate Schwann cell migration and signals that Schwann cells utilize to direct axon regeneration. Understanding the molecular mechanism of Schwann cell migration could potentially offer new therapeutic strategies for peripheral nerve repair.
Topics: Axons; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells
PubMed: 32697392
DOI: 10.1002/glia.23892 -
The Journal of Orthopaedic and Sports... Mar 2023Neurological testing is essential for screening and diagnosing suspected peripheral neuropathies. Detecting changes in somatosensory and motor nerve function can also...
Neurological testing is essential for screening and diagnosing suspected peripheral neuropathies. Detecting changes in somatosensory and motor nerve function can also have direct implications for management decisions. Nevertheless, there is considerable variation in what is included in a bedside neurological examination and how it is performed. Neurological examinations are often used as screening tools to detect neurological deficits but not used to their full potential for monitoring progress or deterioration. Here, we advocate for better use of the neurological examination within a clinical reasoning framework. Constrained by the lack of research in this field, our Viewpoint is based on neuroscientific principles. We highlight 6 challenges for clinicians when conducting neurological examinations and propose ways to overcome these challenges in clinical practice. We challenge widely held ideas about how the results of neurological examinations for peripheral neuropathies are interpreted and how the examinations are performed in practice. .
Topics: Humans; Peripheral Nervous System Diseases; Neurologic Examination; Peripheral Nervous System
PubMed: 36306170
DOI: 10.2519/jospt.2022.11281