Ghrelin increases hippocampal recombination activating gene 1 expression and spatial memory performance in mice.

Ghrelin, which has been shown to improve memory retention, is an endogenous ligand for the growth hormone secretagogue receptor. Recombination activating gene 1 (Rag1), which plays a critical role in the development and maturation of lymphocytes in the immune system, is also expressed in the central nervous system, particularly in the hippocampus, and has been implicated in memory formation. In the current study, the effects of ghrelin on Rag1 expression in the hippocampus and spatial memory performance in wild-type and Rag1 knockout (KO) mice were examined. The Morris water maze test was used to compare the spatial memory performance of wild-type and Rag1-KO mice. Transmission electron microscopy was used to assess morphological changes in synaptic shape and numbers in hippocampal areas after peripheral administration of ghrelin to wild-type and Rag1-KO mice. In wild-type mice, ghrelin increased synaptic vesicles and postsynaptic membrane deposits in the hippocampal CA3 region, shortened water maze escape latencies, and increased platform spans. In Rag1-KO mice, the escape latencies were significantly increased compared with the group of normal mice. Compared with wild-type mice, Rag1-KO mice showed decreasing platform spans. A tendency toward a shortening of the escape latency times and an increase in the platform spans in Rag1-KO mice was observed after ghrelin injection, but this difference was not statistically significant compared with control mice. After the administration of ghrelin, the expression of Rag1 in the hippocampus was significantly increased compared with control mice. Our results suggest that ghrelin potentiates learning and memory in mice, which may be, at least partly, through the regulation of hippocampal Rag1.