The aim of the present study was to examine enhancement of learning and memory by oral administration of ergothioneine (ERGO), which is a hydrophilic antioxidant highly contained in golden oyster mushrooms and other foods, and systemically absorbed by its specific transporter OCTN1/SLC22A4 in daily life, with an aim to clarify its possible role as a neurotropic compound. After oral administration of ERGO in normal mice, the novel object test revealed a longer exploration time for the novel object than for the familiar object. Similar result was also confirmed in mice ingested with ERGO-free diet. Dietary-derived ERGO is present in the body without the administration, but the ERGO administration led to modest (3～4 times) increase in its concentration in plasma and hippocampus. Exposure of cultured hippocampal neurons to ERGO elevated the expression of the synapse formation marker, synapsin I, and neurotrophin-3 and -5. The elevation of synapsin I was inhibited by tropomyosin receptor kinase inhibitor K252a. Thus, oral intake of ERGO may enhance object recognition memory, and this could occur at least partially through promotion of neuronal maturation in the hippocampus.
