Effects of regulating miR-132 mediated GSK-3β on learning and memory function in mice

Exp Ther Med. 2020 Aug;20(2):1191-1197. doi: 10.3892/etm.2020.8768. Epub 2020 May 19.

Abstract

The aimf of this study was to explore effects of miR-132 and glycogen synthase kinase-3β (GSK-3β) on learning and memory in mice. miR-132 inhibitor GSK-3β overexpression agent (sh-GSK-3β) and normal saline (negative control group) were injected into the hippocampus of adult mice, and healthy adult mice were taken as the unrelated control group. The expression of miR-132 and GSK-3β in the hippocampus of adult and elderly mice was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Morris water maze test was employed to detect learning and memory function in mice. The dual luciferase reporter was adopted to determine the relationship between miR-132 and GSK-3β. Compared with the adult group, the expression of miR-132 was significantly downregulated in the hippocampus in the elderly group, while the expression of GSK-3β was upregulated. Injecting miR-132 inhibitor into the hippocampus of adult mice led to a significant increase in escape latency and a significant decrease in the number of times of crossing platforms. The injection of GSK-3β overexpression agent into the hippocampus of adult mice resulted in a marked increase in escape latency and a significant decrease in the number of times of crossing platforms in the water maze test. It was also found that downregulation of GSK-3β reversed the decline in learning and memory in mice caused by downregulation of miR-132 expression. The dual luciferase report identified a targeted regulatory relationship between miR-132 and GSK-3β. Overexpression of miR-132 can inhibit the expression of GSK-3β in mouse learning and memory ability, which provides some inspiration for understanding the occurrence of learning and memory disorders and future treatment methods.

Keywords: glycogen synthase kinase-3β; learning and memory function; miR-132; mice.