Muscarinic Receptor M₃R Signaling Prevents Efficient Remyelination by Human and Mouse Oligodendrocyte Progenitor Cells.

ABSTRACT: Muscarinic receptor antagonists act as potent inducers of oligodendrocyte differentiation and accelerate remyelination. However, the use of muscarinic antagonists in the clinic is limited by poor understanding of the operant receptor subtype, and questions regarding possible species differences between rodents and humans. Based on high selective expression in human oligodendrocyte progenitor cells (OPCs), we hypothesized that M₃R is the functionally relevant receptor. Lentiviral M₃R knockdown in human primary CD140a/PDGFαR⁺ OPCs resulted in enhanced differentiation in vitro and substantially reduced the calcium response following muscarinic agonist treatment. Importantly, following transplantation in hypomyelinating shiverer/rag2 mice, M₃

SUBMITTER: Welliver RR 

PROVIDER: S-EPMC6070663 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature