Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens.

Christopher Kapitza,Rittika Chunder,Katherine S Given,Stefanie Kuerten,Wendy B Macklin,Anja Scheller,Winfried L Neuhuber,Jürgen Wörl,Michael Enders

doi:10.3390/ijms22063233

Abstract

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory, neurodegenerative disease of the central nervous system (CNS) causing myelin sheath destruction
We screened for expression of proteolipid protein (PLP), myelin basic protein (MBP), myelin associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), glial fibrillary acidic protein (GFAP), and oligodendrocytespecific protein (OSP, known as claudin-11)
We found a striking difference in their general arrangement: While GFAP+ -glial cells were mostly related to enteric ganglia and motor endplate contacting efferences, PLP+ -glial cells formed a meshwork of cells pervading the whole organ

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory, neurodegenerative disease of the central nervous system (CNS) causing myelin sheath destruction. Due to the neuronal damage, the signal transmission in the CNS gets disrupted [1,2]. The CNS has been considered to be the primary target of autoimmunity in MS with evidence for antibody-dependent pathomechanisms against CNS myelinand glial-derived antigens in a group of patients [4]. More recent studies have discussed the role of the enteric nervous system (ENS) as a potential target for autoimmunity [5,6], challenging our current understanding of the immunopathogenesis of MS. Dysregulated gastrointestinal functions, anorectal dysfunction, and fecal incontinence in MS patients are examples that may include disruptions in the regulation of the ENS [7,8,9]

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