Trehalose Attenuates Learning and Memory Impairments in Aged Rats via Overexpression of miR-181c.

MicroRNAs have been recognized as important regulators of the aging process. Trehalose, a natural disaccharide, displays protective effects against neuronal impairment through several mechanisms. However, little is known about the interactive effects of aging and trehalose on behavioral function and underlying miRNA expression patterns in the hippocampus of young and old rats. Male Wistar rats were divided into four groups. Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution for 30 days. Two other groups of aged and young rats received regular tap water. At the end of treatment, rats were assessed for cognitive behavior using the Morris water maze test. The expression level of miR-181c and mir-34c was also measured by qRT-PCR. We found that trehalose treatment reduced learning and memory impairment in old rats compared to control old animals (p < 0.05). In contrast, cognitive performance was not significantly improved in trehalose-treated young rats in comparison with young controls (p > 0.05). We also showed that the expression level of miR-181c was significantly increased in trehalose-treated rats (p < 0.01). However, analysis of miR-34c expression level indicated no significant difference between trehalose-treated old rats and non-treated old animals (p > 0.05). Our results indicated that trehalose treatment improved learning and memory function in aged rats by targeting miR-181c. Therefore, trehalose administration may provide a therapeutic strategy to ameliorate age-associated cognitive impairment.