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Abstract Title:

Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway.

Abstract Source:

Mol Neurobiol. 2020 Jun 3. Epub 2020 Jun 3. PMID: 32495180

Abstract Author(s):

Juanjuan Tang, Linyu Lu, Qisheng Wang, Hou Liu, Wenda Xue, Tong Zhou, Liantiao Xu, Kai Wang, Die Wu, Fei Wei, Weiwei Tao, Gang Chen

Article Affiliation:

Juanjuan Tang

Abstract:

Depression is a common non-motor symptom in patients with Parkinson's disease (PD) and difficult to treat. Crocin is a natural multipotential neuroprotective compound that has been shown to elicit antidepressant activity and is promising for the therapy of neuropsychological diseases. Here, we investigated the therapeutic effect of crocin in a mouse model of Parkinson's disease depression (PDD) and clarified the underlying mechanism. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute mouse model of PD, and found that around 60% of the model mice showed depression-like behavior, using the forced swimming test (FST). A regime of 10-day treatment of crocin alleviated the PDD symptoms. The crocin reduced the structural damage in soma volume and axon length of neurons and inhibited their spontaneous discharge in dopaminergic (DA) neurons in the ventral tegmental area (VTA). Notably, the MPTP-treated mice showed the decrease in the critical signaling for synaptic plasticity, including the proteins of PSD-95, synapsin-1, and GluR-1, in the medial prefrontal cortex (mPFC) where it receives efferent from VTA and regulates depression-like behavior. However, crocin treatment rescued the defect of the mammalian target of rapamycin (mTOR) signaling in PDD mice. Furthermore, the antidepressant action of crocin was blunted after blockade of mTOR signaling with the antagonist rapamycin. In conclusion, our study demonstrated that crocin protected the DA projection neurons in the VTA through activating mTOR, which subsequently improved the neural synaptic plasticity of mPFC, and ameliorated depression-like behavior in PD mice.

Study Type : Animal Study

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