Peripheral Nervous System Glia Research Articles

Unveiling the significance of peripheral nervous system glia: implications for nervous system disorders and therapeutic interventions.

Glial cells are indispensable components of the peripheral nervous system (PNS), exerting diverse regulatory functions crucial for neuronal health and function. From myelination and synaptic modulation to immune regulation, glia actively participates in maintaining PNS homeostasis and responding to pathological insults. Further elucidating the roles of glial cells in peripheral nerve disorders holds promise for developing targeted therapeutic interventions to alleviate symptoms and improve patient outcomes. This article reviews the multifaceted functions of PNS glia in shaping nervous system function and their intricate involvement in various neuropathologies, including peripheral neuropathies, neuroinflammatory conditions, and gastrointestinal disorders. Understanding the underlying mechanisms of glial dysfunction offers opportunities for developing targeted therapeutic interventions aimed at preserving nerve function, attenuating neuroinflammation, and restoring gastrointestinal homeostasis. The expanding research on PNS glia underscores their indispensable roles and highlights the potential of therapeutic strategies targeting glial dysfunction in revolutionizing the management of nervous system disorders, offering hope for improved patient outcomes and quality of life.

Beyond Wrapping: Canonical and Noncanonical Functions of Schwann Cells.

Schwann cells in the peripheral nervous system (PNS) are essential for the support and myelination of axons, ensuring fast and accurate communication between the central nervous system and the periphery. Schwann cells and related glia accompany innervating axons in virtually all tissues in the body, where they exhibit remarkable plasticity and the ability to modulate pathology in extraordinary, and sometimes surprising, ways. Here, we provide a brief overview of the various glial cell types in the PNS and describe the cornerstone cellular and molecular processes that enable Schwann cells to perform their canonical functions. We then dive into discussing exciting noncanonical functions of Schwann cells and related PNS glia, which include their role in organizing the PNS, in regulating synaptic activity and pain, in modulating immunity, in providing a pool of stem cells for different organs, and, finally, in influencing cancer.

Charging Up the Periphery: Glial Ionic Regulation in Sensory Perception.

The peripheral nervous system (PNS) receives diverse sensory stimuli from the environment and transmits this information to the central nervous system (CNS) for subsequent processing. Thus, proper functions of cells in peripheral sense organs are a critical gate-keeper to generating appropriate animal sensory behaviors, and indeed their dysfunction tracks sensory deficits, sensorineural disorders, and aging. Like the CNS, the PNS comprises two major cell types, neurons (or sensory cells) and glia (or glia-like supporting neuroepithelial cells). One classic function of PNS glia is to modulate the ionic concentration around associated sensory cells. Here, we review current knowledge of how non-myelinating support cell glia of the PNS regulate the ionic milieu around sensory cell endings across species and systems. Molecular studies reviewed here suggest that, rather than being a passive homeostatic response, glial ionic regulation may in fact actively modulate sensory perception, implying that PNS glia may be active contributors to sensorineural information processing. This is reminiscent of emerging studies suggesting analogous roles for CNS glia in modulating neural circuit processing. We therefore suggest that deeper molecular mechanistic investigations into critical PNS glial functions like ionic regulation are essential to comprehensively understand sensorineural health, disease, and aging.

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease.

The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far greater capacity for regeneration. This difference can be partly attributed to variances in glial-mediated functions, such as axon guidance, structural support, secretion of growth factors and phagocytic activity. Due to their growth-promoting characteristic, transplantation of PNS glia has been trialed for neural repair. After peripheral nerve injuries, Schwann cells (SCs, the main PNS glia) phagocytose myelin debris and attract macrophages to the injury site to aid in debris clearance. One peripheral nerve, the olfactory nerve, is unique in that it continuously regenerates throughout life. The olfactory nerve glia, olfactory ensheathing cells (OECs), are the primary phagocytes within this nerve, continuously clearing axonal debris arising from the normal regeneration of the nerve and after injury. In contrast to SCs, OECs do not appear to attract macrophages. SCs and OECs also respond to and phagocytose bacteria, a function likely critical for tackling microbial invasion of the CNS via peripheral nerves. However, phagocytosis is not always effective; inflammation, aging and/or genetic factors may contribute to compromised phagocytic activity. Here, we highlight the diverse roles of SCs and OECs with the focus on their phagocytic activity under physiological and pathological conditions. We also explore why understanding the contribution of peripheral glia phagocytosis may provide us with translational strategies for achieving axonal regeneration of the injured nervous system and potentially for the treatment of certain neurological diseases.

The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies.

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.

Schwann Cell Exosomes Mediate Neuron-Glia Communication and Enhance Axonal Regeneration.

The functional and structural integrity of the nervous system depends on the coordinated action of neurons and glial cells. Phenomena like synaptic activity, conduction of action potentials, and neuronal growth and regeneration, to name a few, are fine tuned by glial cells. Furthermore, the active role of glial cells in the regulation of neuronal functions is underscored by several conditions in which specific mutation affecting the glia results in axonal dysfunction. We have shown that Schwann cells (SCs), the peripheral nervous system glia, supply axons with ribosomes, and since proteins underlie cellular programs or functions, this dependence of axons from glial cells provides a new and unexplored dimension to our understanding of the nervous system. Recent evidence has now established a new modality of intercellular communication through extracellular vesicles. We have already shown that SC-derived extracellular vesicles known as exosomes enhance axonal regeneration, and increase neuronal survival after pro-degenerative stimuli. Therefore, the biology nervous system will have to be reformulated to include that the phenotype of a nerve cell results from the contribution of two nuclei, with enormous significance for the understanding of the nervous system in health and disease.

Induction and segregation of glial intermediate filament expression in the RT4 family of peripheral nervous system cell lines.

We have found glial fibrillary acidic protein (GFAP), the major component of astrocyte intermediate filaments, to be expressed in cell lines of the RT4 peripheral neurotumor family. The RT4 family is a "stem-cell-like" cell line, RT4-AC, that spontaneously undergoes differentiation in culture to three derivative cell types. This process, termed cell-type conversion, results in a segregation among the derivative cell types of parental cell phenotypes that have been described as neuronal-like or glial-like. We have identified a 50-kDa GFAP-immunoreactive cytoskeletal protein and GFAP mRNA in continuous RT4-AC and RT4-D (glial-type derivative) cell lines, but not in two presumptive neuronal-type cell lines. This result suggests that GFAP gene expression is coordinately coupled with the expression of other glial properties during cell-type conversion. In addition, the RT4-AC and RT4-D sublines were found to significantly express GFAP only at high cell densities and not during logarithmic growth and to express GFAP precociously during morphological differentiation following treatment with 1 mM N6, O2'-dibutyryladenosine 3',5'-cyclic monophosphate. These observations closely reflect reports of glial filament expression in astrocyte cultures, suggesting that a common regulatory mechanism is employed by central and peripheral nervous system glia.