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Glia Dec 2022Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the...
Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.
Topics: Ion Channels; Myelin Sheath; Neurogenesis; Schwann Cells
PubMed: 35903933
DOI: 10.1002/glia.24251 -
Progress in Neurobiology Jan 2022Peripheral nerve injuries result in disrupted cellular communication between the central nervous system and somatic distal end targets. The peripheral nervous system is... (Review)
Review
Peripheral nerve injuries result in disrupted cellular communication between the central nervous system and somatic distal end targets. The peripheral nervous system is capable of independent and extensive regeneration; however, meaningful target muscle reinnervation and functional recovery remain limited and may result in chronic neuropathic pain and diminished quality of life. Macrophages, the primary innate immune cells of the body, are critical contributors to regeneration of the injured peripheral nervous system. However, in some clinical scenarios, macrophages may fail to provide adequate support with optimal timing, duration, and location. Here, we review the history of immunosuppressive and immunomodulatory strategies to treat nerve injuries. Thereafter, we enumerate the ways in which macrophages contribute to successful nerve regeneration. We argue that implementing macrophage-based immunomodulatory therapies is a promising treatment strategy for nerve injuries across a wide range of clinical presentations.
Topics: Humans; Nerve Regeneration; Neuroimmunomodulation; Peripheral Nerve Injuries; Peripheral Nerves; Quality of Life
PubMed: 34492307
DOI: 10.1016/j.pneurobio.2021.102172 -
Cells Sep 2020Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases.... (Review)
Review
Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.
Topics: Animals; Astrocytes; Brain Infarction; Brain Injuries, Traumatic; Carbon Monoxide Poisoning; Cell Communication; Central Nervous System; Glycolysis; Humans; Macrophage Activation; Macrophages; Microglia; Nerve Regeneration; Neurons; Oxidative Phosphorylation; Peripheral Nerve Injuries; Peripheral Nervous System; Reactive Oxygen Species
PubMed: 32967118
DOI: 10.3390/cells9092132 -
Cleveland Clinic Journal of Medicine Nov 2020Electrodiagnostic testing, consisting of nerve conduction studies and needle electrode examination, serves as an extension of a neurologic examination for evaluating a... (Review)
Review
Electrodiagnostic testing, consisting of nerve conduction studies and needle electrode examination, serves as an extension of a neurologic examination for evaluating a variety of focal and generalized neuromuscular conditions. By providing important clues on location, chronicity, severity, and pathophysiology, it can help to establish a diagnosis, evaluate the need for surgery, and assess patients who do not improve as expected after surgery.
Topics: Electrodiagnosis; Humans; Neuromuscular Diseases; Peripheral Nervous System; Peripheral Nervous System Diseases; Signal Processing, Computer-Assisted
PubMed: 33139261
DOI: 10.3949/ccjm.87a.19154 -
Neuroscience Letters Jan 2021Neurons are polarized cells whose fundamental functions are to receive, conduct and transmit signals. In bilateral animals, the nervous system is divided into the... (Review)
Review
Neurons are polarized cells whose fundamental functions are to receive, conduct and transmit signals. In bilateral animals, the nervous system is divided into the central (CNS) and peripheral (PNS) nervous system. The main function of the PNS is to connect the CNS to the limbs and organs, essentially serving as a relay between the brain and spinal cord and the rest of the body. Sensory axons can be up to 3 feet in length. Because of its long-reaching and complex structure, the peripheral nervous system (PNS) is exposed and vulnerable to many genetic, metabolic and environmental predispositions. Lipids and lipid intermediates are essential components of nerves. About 50 % of the brain dry weight consist of lipids, which makes it the second highest lipid rich tissue after adipose tissue. However, the role of lipids in neurological disorders in particular of the peripheral nerves is not well understood. This review aims to provide an overview about the role of lipids in the disorders of the PNS.
Topics: Animals; Humans; Lipid Metabolism; Lipids; Neurons; Peripheral Nervous System; Peripheral Nervous System Diseases
PubMed: 33166639
DOI: 10.1016/j.neulet.2020.135455 -
Cell Reports Sep 2023Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We...
Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:peripheral nervous system (PNS) borderline where OPCs are absent. Most axons stop in contact with a dense network of OPC processes. Live imaging, immuno-electron microscopy (immuno-EM), and OPC-dorsal root ganglia (DRG) co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.
Topics: Mice; Animals; Oligodendrocyte Precursor Cells; Spinal Cord; Axons; Spinal Nerve Roots; Ganglia, Spinal; Nerve Regeneration
PubMed: 37656624
DOI: 10.1016/j.celrep.2023.113068 -
Current Neurology and Neuroscience... Dec 2022Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and... (Review)
Review
PURPOSE OF REVIEW
Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies.
RECENT FINDINGS
Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical-physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.
Topics: Humans; Autonomic Nervous System Diseases; Blood Pressure Monitoring, Ambulatory; Peripheral Nervous System Diseases; Autonomic Nervous System; Norepinephrine; Diabetic Neuropathies
PubMed: 36376534
DOI: 10.1007/s11910-022-01240-4 -
Frontiers in Immunology 2022The central nervous system is the most important nervous system in vertebrates, which is responsible for transmitting information to the peripheral nervous system and... (Review)
Review
The central nervous system is the most important nervous system in vertebrates, which is responsible for transmitting information to the peripheral nervous system and controlling the body's activities. It mainly consists of the brain and spinal cord, which contains rich of neurons, the precision of the neural structures susceptible to damage from the outside world and from the internal factors of inflammation infection, leading to a series of central nervous system diseases, such as traumatic brain injury, nerve inflammation, etc., these diseases may cause irreversible damage on the central nervous or lead to subsequent chronic lesions. After disease or injury, the immune system of the central nervous system will play a role, releasing cytokines to recruit immune cells to enter, and the immune cells will differentiate according to the location and degree of the lesion, and become specific immune cells with different functions, recognize and phagocytose inflammatory factors, and repair the damaged neural structure. However, if the response of these immune cells is not suppressed, the overexpression of some genes can cause further damage to the central nervous system. There is a need to understand the molecular mechanisms by which these immune cells work, and this information may lead to immunotherapies that target certain diseases and avoid over-activation of immune cells. In this review, we summarized several immune cells that mainly play a role in the central nervous system and their roles, and also explained the response process of the immune system in the process of some common neurological diseases, which may provide new insights into the central nervous system.
Topics: Animals; Central Nervous System Diseases; Central Nervous System; Immune System; Peripheral Nervous System; Inflammation
PubMed: 36466889
DOI: 10.3389/fimmu.2022.1063928 -
International Journal of Molecular... Dec 2023Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules,... (Review)
Review
Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules, which orchestrate essential biological processes, including cell differentiation, proliferation, and survival, in the recipient cells. These bioactive properties of exosomes render them a promising choice for therapeutic use in the realm of tissue regeneration and repair. Exosomes possess notable positive attributes, including a high bioavailability, inherent safety, and stability, as well as the capacity to be functionalized so that drugs or biological agents can be encapsulated within them or to have their surface modified with ligands and receptors to imbue them with selective cell or tissue targeting. Remarkably, their small size and capacity for receptor-mediated transcytosis enable exosomes to cross the blood-brain barrier (BBB) and access the central nervous system (CNS). Unlike cell-based therapies, exosomes present fewer ethical constraints in their collection and direct use as a therapeutic approach in the human body. These advantageous qualities underscore the vast potential of exosomes as a treatment option for neurological injuries and diseases, setting them apart from other cell-based biological agents. Considering the therapeutic potential of exosomes, the current review seeks to specifically examine an area of investigation that encompasses the development of Schwann cell (SC)-derived exosomal vesicles (SCEVs) as an approach to spinal cord injury (SCI) protection and repair. SCs, the myelinating glia of the peripheral nervous system, have a long history of demonstrated benefit in repair of the injured spinal cord and peripheral nerves when transplanted, including their recent advancement to clinical investigations for feasibility and safety in humans. This review delves into the potential of utilizing SCEVs as a therapy for SCI, explores promising engineering strategies to customize SCEVs for specific actions, and examines how SCEVs may offer unique clinical advantages over SC transplantation for repair of the injured spinal cord.
Topics: Humans; Spinal Cord; Spinal Cord Injuries; Schwann Cells; Peripheral Nerves; Neuroglia; Exosomes
PubMed: 38139147
DOI: 10.3390/ijms242417317 -
Experimental Neurology Jan 2021Stroke elicits excessive immune activation in the injured brain tissue. This well-recognized neural inflammation in the brain is not just an intrinsic organ response but... (Review)
Review
Stroke elicits excessive immune activation in the injured brain tissue. This well-recognized neural inflammation in the brain is not just an intrinsic organ response but also a result of additional intricate interactions between infiltrating peripheral immune cells and the resident immune cells in the affected areas. Given that there is a finite number of immune cells in the organism at the time of stroke, the partitioned immune systems of the central nervous system (CNS) and periphery must appropriately distribute the limited pool of immune cells between the two domains, mounting a necessary post-stroke inflammatory response by supplying a sufficient number of immune cells into the brain while maintaining peripheral immunity. Stroke pathophysiology has mainly been neurocentric in focus, but understanding the distinct roles of the CNS and peripheral immunity in their concerted action against ischemic insults is crucial. This review will discuss stroke-induced influences of the peripheral immune system on CNS injury/repair and of neural inflammation on peripheral immunity, and how comorbidity influences each.
Topics: Animals; Brain Ischemia; Central Nervous System; Humans; Immunity, Cellular; Ischemic Stroke; Peripheral Nervous System
PubMed: 33065078
DOI: 10.1016/j.expneurol.2020.113508