Abstract:

Objective To study the effect of TRPM2 gene knockout（TRPM2-/-）on lipopolysaccharide （LPS）induced depressive ⁃like behavior and related mechanisms. Methods Male TRPM2-/- mice were divided into TRPM2-/- group（n = 30）and TRPM2-/-+LPS group（n = 30）；male wild type（WT）homogenotypic mice were divided into WT group（n = 30）and WT+LPS group（n = 30）. Then the levels of 5⁃hydroxytryptamine（5⁃HT）， TNF⁃α and IL⁃1β in hippocampus and/or prefrontal cortex were measured by ELISA assay. Expressions of neuronal and glial cell markers were observed by immunofluorescent staining. The protein levels of p⁃GSK3β and t⁃GSK3β were detected by Western Blot and the depressive ⁃like behavior was measured by tail suspension test and forced swim test. Results Compared with that of WT + LPS group，the concentration of 5⁃HT in the hippocampus of TRPM2-/-+LPS group was decreased（P＜0.05）；the number of cells expressing GFAP and Iba⁃1 in the hippocam⁃ pus of TRPM2-/-+LPS group was decreased（P＜0.01）；the expressions of TNF⁃α and IL⁃1β in the hippocampus of TRPM2-/-+LPS group were also decreased（P＜0.01）but the protein level of p⁃GSK3β was increased（P＜0.01）. No differences of t⁃GSK3β protein level was found in the hippocampus of TRPM2-/-+LPS group when compared with the WT+LPS group. Moreover，the mobility time in tail suspension test and forced swim test of the TRPM2-/-+LPS group were significantly shortened（P＜0.05）when compared with the WT + LPS group. Conclusion TRPM2 knockout can improve LPS induced depressive⁃like behavior in mice，and it may be correlated with the increased level of p⁃GSK3β in hippocampus.

Key words:

TRPM2, lipopolysaccharide, depressive?like behavior, p?GSK3β