Functional Characterization of Muscarinic Receptors in Human Schwann Cells

Abstract

Functional characterization of muscarinic cholinergic receptors in myelinating glial cells has been well described both in central and peripheral nervous system. Rat Schwann cells (SCs) express different muscarinic receptor subtypes with the prevalence of the M2 subtype. The selective stimulation of this receptor subtype inhibits SC proliferation, improving their differentiation towards myelinating phenotype. In this work, we describe for the first time that human SCs are cholinoceptive as they express several muscarinic receptor subtypes and, as for rat SCs, M2 receptor is one of the most abundant. Human SCs, isolated from adult nerves, were cultured in vitro and stimulated with M2 muscarinic agonist arecaidine propargyl ester (APE). Similarly to that observed in rat, M2 receptor activation causes a decreased cell proliferation and promotes SC differentiation as suggested by increased Egr2 expression with an improved spindle-like shape cell morphology. Conversely, the non-selective stimulation of muscarinic receptors appears to promote cell proliferation with a reduction of SC average cell diameter. The data obtained demonstrate that human SCs are cholinoceptive and that human cultured SCs may represent an interesting tool to understand their physiology and increase the knowledge on how the cholinergic stimulation may contribute to address human SC development in normal and pathological conditions.

Clemastine improves electrophysiologic and histomorphometric changes through promoting myelin repair in a murine model of compression neuropathy

“…Schwann cells are the main glial cells in the PNS and play an essential role in the insulation of axons by forming myelin, resulting in fast propagation of action potentials. Schwann cells also express the M1–M4 subtypes of muscarinic receptors on their membrane 10 , 11 . The muscarinic receptor type expressed on Schwann cells could differently mediate Schwann cell proliferation through M1 and/or M3 or differentiation, but mainly through the M2 subtype 17 , 19 , 20 .…”

“…Evidence suggests that this remyelination effect of clemastine is mediated by off-target antimuscarinic action at the muscarinic acetylcholine receptor on OPCs 6 , 9 . Schwann cells are the main glial cells in the PNS and also express M1, M2, M3, and M4 muscarinic receptors 10 , 11 . Clemastine is expected to promote Schwann cell-mediated myelin repair, as in previous reports of central nervous system (CNS) demyelinating disease.…”

Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure

“…All procedures were approved by the National Research Ethics Committee, the UK (NRES 18/NW/0847) and conformed with the World Medical Association Declaration of Helsinki. Primary naïve human SC were obtained as per Piovesana et al [ 17 ]. Briefly, nerves were dissected, and single extracted fibers were cut into small pieces, then cultured in 60 cm 2 dishes with SC media supplemented with 10 µM fsk and 100 ng/mL glial growth factor 2 (GGF-2, Acorda Therapeutics, Ardsley, NY, USA) for two weeks.…”

The Mechanisms Mediated by α7 Acetylcholine Nicotinic Receptors May Contribute to Peripheral Nerve Regeneration

“…Previous studies demonstrated that different neurotransmitters may control and modulate a variety of biological processes during development as well as adult life physiology [5][6][7]. In particular, it has been shown that both rat and human SCs express muscarinic acetylcholine receptors (mAChRs) and are thus able to respond to acetylcholine (ACh) stimuli [8][9][10][11]. The selective activation of specific mAChRs, such as the M2 subtype, regulates some aspects of the SCs development [8][9][10][11] as well as those mechanisms aimed at enhancing their regenerative capability, modulating the production and release of the nerve growth factor (NGF) [12].…”

“…In particular, it has been shown that both rat and human SCs express muscarinic acetylcholine receptors (mAChRs) and are thus able to respond to acetylcholine (ACh) stimuli [8][9][10][11]. The selective activation of specific mAChRs, such as the M2 subtype, regulates some aspects of the SCs development [8][9][10][11] as well as those mechanisms aimed at enhancing their regenerative capability, modulating the production and release of the nerve growth factor (NGF) [12]. Therefore, the cholinergic system could be a putative target for identifying novel pharmacological treatments to speed up the regeneration process.…”