Effect and mechanism of melatonin on astrocyte polarization in rats with mental disorder
Objective To explore the mechanism of melatonin in regulating astrocytes polarization in rats with mental disorders based on Nrf2-HO-1/CYP2E1 pathway.Methods Fifty rats were randomly divided into sham group,model group,melatonin group,Nrf2 inhibitor(ML-385)group and melatonin+ML-385 group.The frontal cortex of rats were damaged by blade cutting to establish a mental disorder model.The behavioral changes of rats were detected by sucrose preference and open field experiment.The pathological damage and neuronal damage of the frontal cortex was observed by HE and Nissl staining.The expressions of GABAergic neuron marker GAD67,C3/GFAP and S100A10/GFAP in A1 and A2 type astrocytes were detected by immunofluorescence staining.The expressions of CXCR7,PI3K,Akt,p-PI3K and p-Akt proteins were detected by Western blot.Results Compared with the model group,the sugar water preference index,the number of crossing cells and the number of standing times of rats in the melatonin group were significantly increased,the pathological damage of the frontal cortex was alleviated,the number of neurons was significantly increased,the expression of GAD67 in the frontal cortex of rats was significantly increased,the expression of C3/GFAP was significantly decreased,and the expression of S100A10/GFAP was significantly increased,the expressions of Nrf2 and HO-1 protein were significantly increased,while the expression of CYP2E1 was significantly decreased.However,the above effects of melatonin on rats with mental disorders were weakened or inhibited by ML-385.Conclusion Melatonin might promote the astrocytes polarization of A1 to A2 by regulating Nrf2-HO-1/CYP2E1 pathway,and thus improve the mental disorders in rats.
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