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 Ca 2+ 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 Ca 2+ 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.

The previous study demonstrated that hot water extract of golden oyster mushrooms (Aminothioneine®) and ergothioneine, which is a hydrophilic antioxidant and contained at high levels in golden oyster mushrooms, increased neuronal differentiation in the hippocampal dentate gyrus of mice and have antidepressant-like effects in mice. Here, we investigated the effect of Aminothioneine on BDNF expression in primary cultures of cortical cells and learning and memory in mice. In primary cultures of rat cortical cells, Aminothioneine, but not ergothioneine, significantly increased expression levels of BDNF mRNA. Aminothioneine also increased the levels of BDNF expression in the hippocampus of mice. Aminothioneine significantly increased freezing behavior in the test session of the contextual fear conditioning test. In the test session of the novel object location recognition test, Aminothioneine-administered mice spent more time exploring the object at the novel location. Taken together, Aminothioneine increased expression levels of BDNF in cultured neurons and hippocampus of mice. Also, Aminothioneine enhances learning and memory in mice. Because it has been reported that higher expression levels of BDNF are associated with slower cognitive decline during aging, Aminothioneine could act as a memory stabilizer in an aging brain.