Shouhui Tongbian Capsule Alleviates Depressive-Like Behavior in A Mouse Model of Parkinson's Disease Depression

摘要

Objective:To evaluate the anti-depressive effects of Shouhui tongbian capsule(SHTB) in a mouse model of Parkinson's disease depression(PDD) in vivo and explore its underlying mechanism. Methods: The antidepressant effects of SHTB was tested in a mouse model of PDD. the PDD mouse model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP, 30 mg/kg) for 5 consecutive days followed by chronic unpredictable mild stress(CUMS) for 3 weeks from the 21 th day after MPTP. The mice were divided into the following three groups: Control group, MPTP+CUMS group, and MPTP+CUMS+SHTB 200 mg/kg group. The mice underwent behavior studies to examine the effects of SHTB on motor dysfunction and the depressive-like behavior changes. Immunostaining and Western blot analysis of tyrosine hydroxylase(TH) were performed to determine the nigrostriatal dopaminergic neurodegeneration. Immunofluorescence and RT-qPCR were performed to evaluate the glial activation and mRNA levels of pro-inflammatory cytokines in the mice hippocampus and substantia nigra. Golgi staining and Western blot analysis were used to examine the synaptic changes in mice hippocampus. HE staining and Immunofluorescence were used to evaluate the intestinal barrier changes. Results: The PDD mice showed motor dysfunction and depressive-like behaviors. PDD mice also exhibited nigrostriatal dopaminergic neurodegeneration, increased proinflammatory responses and synaptic damage in the hippocampus. Daily administration of SHTB in mice significantly reduced the depressive-like behaviors in PDD mice as evidenced by increased sucrose consumption in the sucrose preference test(SPT), decreased immobility time in the forced swimming test(FST), and increased time spent in open arms in the elevated plus maze(EPM) test. SHTB also ameliorated MPTP-induced dopaminergic neurotoxicity and motor deficits in PDD mice. The glial cell activation and the production of proinflammatory cytokines were also attenuated by SHTB treatment in mice brain. Moreover, SHTB prevented the synaptic injury in the hippocampus of PDD mice. Further study revealed that SHTB ameliorated gut barrier dysfunction in PDD mice. Conclusion: SHTB showed anti-depressant potential in PDD mice possibly by alleviating neuroinflammation and synaptic dysfunction. SHTB may target both the motor and non-motor symptoms of PD.

关键词

Parkinson's disease depression / Shouhui tongbian capsule / neuroinflammation / synapse