ReferenceID 4983

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

Mol Neurobiol

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

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Reference Id
4983
Evidence Id
21573
Core Evidence Id
21573
Source Reference Id
3215
Herb2 Reference Id
HBREF004012
Subject Paper Key
HBIN021714_32495180
Pubmed Id
32495180
Doi
10.1007/s12035-020-01941-2
Paper Title
Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway
Paper 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.
Journal
Mol Neurobiol
Publish Year
2020
Experiment Subject
mouse; patient
Experiment Type
Animal Experiment
Phenotype Related
Neuropsychological Diseases; Parkinson's Disease Depression; Parkinson's Disease
Paper Title Cn
Paper Title En
Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway
Bilingual Status
semi_complete