Regulation of capsaicin receptor TRPV1 on depressive behavior and neuronal autophagy in cerebral ischemia-reperfusion mice / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the effect and molecular mechanism of capsaicin receptor(TRPV1) on neuronal autophagy and depression-like behavior in mice.Methods:Using the method of random number table, 87 C57 male mice were divided into Sham operation group (Sham group), cerebral ischemia/reperfusion group (I/R group) and capsazepine(CPZ) preconditioning cerebral ischemia/reperfusion group (I/R+ CPZ group), with 28 mice in each group due to 3 incompatible.Mice in the I/R group were subjected to right middle cerebral artery occlusion (MCAO) to establish a cerebral ischemia-reperfusion model.Mice in the I/R+ CPZ group were injected with CPZ in the lateral ventricle prior to moulding.Mice in the Sham group had only wire plugs inserted and no arterial embolization was performed.The mNSS score was used to evaluate the degree of neurological deficits.The depression-like behaviour of mice was detected by the tail suspension test and forced swimming test.The infarct volume was observed by TTC staining.The pathological changes in the amygdala were observed by HE staining, and the expression of Beclin-1, LC3, p62 and p-PI3K, p-AKT and p-mTOR proteins were detected by Western blot.Statistical analysis was performed using SPSS 23.0 software.The t-test was used for comparison between two groups and one-way ANOVA was used for comparison of multiple group. Results:The neurological deficit score in I/R+ CPZ group (9.77±2.32) was significantly lower than that in I/R group (12.85±2.73) ( t=3.10, P<0.01). Compared with I/R group, the tail suspension immobility time of I/R+ CPZ Group ((93.28±50.69)s, (143.80±35.61) s; t=2.94, P<0.01) and the forced swimming immobility time ((139.50±13.33)s, (175.30±19.78)s; t=2.94, P<0.01) were significantly reduced.The results of TTC staining showed that the cerebral infarct volume in I/R+ CPZ group was significantly lower than that in I/R group ((19.30±5.19)%, (33.60±3.90)%; t=5.40, P<0.01). HE staining showed that the number of cells in the amygdala region of mice in the I/R+ CPZ group increased compared with that in the I/R group, with tighter arrangement and reduced deep staining of nuclear fixation.Western blot showed that compared with I/R group, the expression levels of autophagy related proteins Beclin-1( t=2.94, P<0.05) and LC3 ( t=3.16, P<0.05) in amygdala of I/R+ CPZ group were down-regulated, while the expression levels of p62( t=3.60, P<0.05), p-PI3K ( t=7.79, P<0.01), p-AKT ( t=4.15, P<0.01) and p-mTOR ( t=6.15, P<0.01) were up-regulated. Conclusion:Cerebral ischemia/reperfusion activates neuronal autophagy, and CPZ may regulate the PI3K-AKT-mTOR pathway, thus inhibits excessive activation of autophagy, thereby acting as a neuroprotective agent and improving post-stroke depression-like behaviour.