Acetylcholine suppresses the increase of glia fibrillary acidic protein expression via acetylcholine receptors in cAMP-induced astrocytic differentiation of rat C6 glioma cells

Neurosci Lett. 2019 Apr 17:698:146-153. doi: 10.1016/j.neulet.2019.01.020. Epub 2019 Jan 9.

Abstract

Astrocytes, the most common glial cells in the central nervous system, maintain neuronal functions and have roles in neurological diseases. Acetylcholine (ACh) is one of the most essential neurotransmitters, and ACh receptor (AChR) ligands were recently reported to influence astrocyte functions. However, the functions of ACh, the only endogenous agonist of AChR, in astrocytogenesis and in the expression of astrocytic marker genes have not been known. We previously demonstrated that the inhibition of acetylcholine esterase (AChE) suppressed the differentiation of rat glioma C6 cells, an astrocyte differentiation model, and we observed a suppressive effect of ACh agonists on astrocyte differentiation. Our present study revealed that in the cAMP-induced differentiation of C6 cells, an AChR antagonist alleviated the expression of glia fibrillary acidic protein (GFAP) that had been suppressed by dichlorvos (DDVP), an organophosphate and an AChE inhibitor. Our findings also demonstrated a direct effect of ACh on the GFAP expression, and that muscarinic AChR is involved in the suppressive effect of ACh on the GFAP expression in differentiation-induced C6 cells. This is the first report indicating that ACh the only endogenous agonist for AChRs functions as a mediator of astrocyte differentiation.

Keywords: Acethylcholine; Astrocyte; Differentiation; GFAP; Muscarinic acetylcholine receptor; Prolifelation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology*
  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cholinergic Agents / pharmacology
  • Cyclic AMP / metabolism
  • Glial Fibrillary Acidic Protein / metabolism*
  • Glioma / drug therapy
  • Glioma / metabolism
  • Intermediate Filaments / metabolism
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Rats
  • Receptors, Cholinergic / drug effects*
  • Receptors, Cholinergic / metabolism

Substances

  • Cholinergic Agents
  • Glial Fibrillary Acidic Protein
  • Receptors, Cholinergic
  • Cyclic AMP
  • Acetylcholine