Background: The enhancement of learning and memory through food-derived ingredients
is of great interest to healthy individuals as well as those with diseases. Ergothioneine (ERGO)
is a hydrophilic antioxidant highly contained in edible golden oyster mushrooms (Pleurotus
cornucopiae var. citrinopileatus), and systemically absorbed by its specific transporter, carnitine/organic
cation transporter OCTN1/SLC22A4.
Objective: This study aims to examine the possible enhancement of object recognition memory by
oral administration of ERGO in normal mice.
Methods: Novel object recognition test, spatial recognition test, LC-MS/MS, Golgi staining, neuronal
culture, western blotting, immunocytochemistry, and quantitative RT-PCR were utilized.
Result: After oral administration of ERGO (at a dose of 1–50 mg/kg) three times per week for two
weeks in ICR mice, the novel object recognition test revealed a longer exploration time for the novel
object than for the familiar object. After oral administration of ERGO, the spatial recognition
test also revealed a longer exploration time for the spatially moved object than the unmoved one in
mice fed ERGO-free diet. The discrimination index was significantly higher in the ERGO-treated
group than the control in both behavioral tests. ERGO administration led to an increase in its concentration
in the plasma and hippocampus. The systemic concentration reached was relevant to
those found in humans after oral ERGO administration. Golgi staining revealed that ERGO administration
increased the number of matured spines in the hippocampus. Exposure of cultured hippocampal
neurons to ERGO elevated the expression of the synapse formation marker, synapsin I.
This elevation of synapsin I was inhibited by the tropomyosin receptor kinase inhibitor, K252a.
Treatment with ERGO also increased the expression of neurotrophin-3 and -5, and phosphorylated
mammalian target of rapamycin in hippocampal neurons.
Conclusion: Oral intake of ERGO may enhance object recognition memory at its plasma concentration
achievable in humans, and this enhancement effect could occur, at least in part, through the
promotion of neuronal maturation in the hippocampus.