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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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) is a principal factor for neurogenesis, neurodevelopment and neural survival through a BDNF receptor, tropomyosin-related kinase (Trk) B, while BDNF can also cause a decrease in the intracellular glutathione (GSH) level. We investigated the exacerbation of methylmercury-induced death of rat cerebellar granular neurons (CGNs) by BDNF in vitro. Since methylmercury can decrease intracellular GSH levels, we hypothesized that a further decrease of the intracellular GSH level is involved in the process of the exacerbation of neuronal cell death. In the present study, we established that in CGN culture, a decrease of the intracellular GSH level was further potentiated with BDNF in the process of the methylmercury-induced neuronal death and also in GSH reducer-induced neuronal death. BDNF treatment promoted the decrease in GSH levels induced by methylmercury and also by L-buthionine sulfoximine (BSO) and diethyl maleate (DEM). The promoting effect of BDNF was observed in a TrkB-vector transformant of the rat neuroblastoma B35 cell line but not in the mock-vector transformant. These results indicate that the exacerbating effect of BDNF on methylmercury-induced neuronal death in cultures of CGNs includes a further decrease of intracellular GSH levels, for which TrkB is essential.