[Resistance exercise regulates hippocampal microglia polarization through TREM2/NF-κB/STAT3 signal pathway to improve cognitive dysfunction in T2DM mice].

Abstract

The study aimed to explore the effect and mechanism of resistance exercise (RE) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) mice. Six 8-week-old male m/m mice were used as control (Con) group, and db/db mice of the matched age were randomly divided into model control (db/db) group and db+RE group, with 6 mice in each group. The db+RE group was given 8 weeks of resistance climbing ladder exercise intervention. The fasting blood glucose and body weight of the mice were measured weekly. After the intervention, the spatial learning and memory of the mice were detected by Morris water maze, and the neuronal damage in the hippocampus of the mice was detected by Nissl staining. The protein expression levels of PSD93, PSD95, BDNF, CREB, p-CREB, IL-6, IL-1β, TNF-α, Iba-1, iNOS, CD206, Arg1, triggering receptor expressed on myeloid cells 2 (TREM2), NF-κB, p-STAT3, and STAT3 were detected by Western blot. The mRNA expression levels of inflammatory factors and TREM2 in hippocampus were evaluated by qRT-PCR, and the expression and localization of Iba-1, CD206, CD86, and TREM2 were determined by immunofluorescence staining. The results showed that the spatial learning and memory of the db/db group were significantly declined, the neurons in the hippocampus were damaged, the protein levels of PSD93, PSD95, BDNF, CD206, Arg1, TREM2 and the ratio of p-CREB/CREB were significantly down-regulated, the mRNA and protein expression levels of IL-6, IL-1β and TNF-α were significantly up-regulated, and the protein levels of iNOS, Iba-1, NF-κB and the ratio of p-STAT3/STAT3 were significantly increased compared with the Con group. However, the 8-week RE improved the spatial learning and memory of db/db mice, alleviated the damage of hippocampal neurons, promoted the polarization of M2 microglia, and inhibited the neuroinflammation. The above results suggest that RE can improve cognitive dysfunction in T2DM mice, and its mechanism may be related to regulating microglia polarization via TREM2/NF-κB/STAT3 signaling pathway.