Abstract
Ameliorating reduced brain-derived neurotrophic factor (BDNF) expression or maintaining high BDNF levels in the brain has been suggested to improve brain function in neurological diseases and prevent aging-related brain dysfunction. In this study, we found that a food-derived product, Aminothioneine® (AT), which is prepared from the extract of golden oyster mushrooms (Pleurotus cornucopiae var. citrinopileatus), increased Bdnf mRNA expression levels in primary rat cortical neuron cultures. Ergothioneine (ET) comprises more than 1% in AT and is an active constituent of AT, and ET has been reported to increase neurotrophin-4/5, but not BDNF, expression levels in neural stem cells. ET also did not affect Bdnf mRNA expression in cultured cortical neurons, suggesting that AT contains other active constituents that induce Bdnf mRNA expression in neurons. AT-induced Bdnf mRNA expression was completely blocked by d-(-)-2-Amino-5-phosphonopentanoic acid but partially blocked by nicardipine, U0126, and FK506. This result suggested that N-methyl-d-aspartate receptor-derived Ca2+ signals, including those mediated by extracellular signal-regulated kinase/mitogen-activated protein kinase and calcineurin, are the main contributors to Bdnf mRNA induction. In addition, AT increased cAMP-response element-binding protein (CREB) phosphorylation and the nuclear localization of CREB-regulated transcriptional coactivator 1 in neurons. Thus, AT can increase Bdnf mRNA expression via Ca2+ signal-induced CREB-dependent transcription in neurons. Because AT is a food-derived product, increasing and/or maintaining BDNF levels in the brain by daily intake of the product could be possible, which may be beneficial for neurological and aging-related disorders.