Stimulation of α7 nicotinic acetylcholine receptor regulates glutamate transporter GLAST via basic fibroblast growth factor production in cultured cortical microglia

Brain Research
Norimitsu MoriokaYoshihiro Nakata

Abstract

The α7 nicotinic acetylcholine (nACh) receptor expressed in microglia has a crucial role in neuroprotection. Simulation of α7 nACh receptor leads to increased expression of glutamate/aspartate transporter (GLAST), which in turn decreases synaptic glutamate levels. However, the upregulation of GLAST in cultured rat cortical microglia appears long after (over 18 h) stimulation of the α7 nACh receptor with nicotine. Thus, the current study elucidated the pathway responsible for the induction of GLAST expression in cultured cortical microglia. Nicotine-induced GLAST mRNA expression was significantly inhibited by cycloheximide pretreatment, indicating that a protein intermediary, such as a growth factor, is required for GLAST expression. The expression of fibroblast growth factor-2 (FGF-2) mRNA in cortical microglia was significantly increased 6 and 12h after treatment with nicotine, and this increase was potently inhibited by pretreatment with methyllycaconitine, a selective α7 nACh receptor antagonist. The treatment with nicotine also significantly increased FGF-2 protein expression. Furthermore, treatment with recombinant FGF-2 increased GLAST mRNA, protein expression and (14)C-glutamate uptake, a functional measurement of GLAST ...Continue Reading

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Citations

Jun 5, 2020·The Journal of Experimental Medicine·Shih-Ying WuKounosuke Watabe
Jun 13, 2017·The International Journal of Neuropsychopharmacology·Sade Spencer, Peter W Kalivas
May 8, 2021·Scientific Reports·Chiara D'AngeloMarcella Reale
May 11, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ari DienelDevin W McBride

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