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Synergistic effect of electric stimulation and mesenchymal stem cells against Parkinson's disease.

ABSTRACT: Electroconvulsive therapy (ECT) has known beneficial effects on the core motor symptoms of Parkinson's disease (PD), likely through induction of dopamine release and sensitivity of dopamine receptors. Mesenchymal stem cells (MSCs) can salvage loss of dopamine in PD through their differentiation into dopaminergic neurons. However, it is not known if combined ECT and MSC transplantation may have a synergistic effect against PD. Here, we showed that ECT significantly increased the differentiation of the transplanted MSCs into dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. On the other hand, transplantation of MSCs significantly increased dopamine levels after ECT. Co-application of ECT and MSC transplantation generated a synergistic effect through increases in dopamine and decreases in pro-inflammatory cytokines, resulting in significantly attenuated defect in stepping test and rotational behavior in MPTP-mice. Together, our data suggest that combined ECT and MSC transplantation can be a valuable treatment of PD.

SUBMITTER: Yang C

PROVIDER: S-EPMC7485716 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synergistic effect of electric stimulation and mesenchymal stem cells against Parkinson's disease.

Yang Chunhui C Qiu Yiqing Y Qing Yuan Y Xu Jinyu J Dai Wei W Hu Xiaowu X Wu Xi X

Aging 20200824 16

Electroconvulsive therapy (ECT) has known beneficial effects on the core motor symptoms of Parkinson's disease (PD), likely through induction of dopamine release and sensitivity of dopamine receptors. Mesenchymal stem cells (MSCs) can salvage loss of dopamine in PD through their differentiation into dopaminergic neurons. However, it is not known if combined ECT and MSC transplantation may have a synergistic effect against PD. Here, we showed that ECT significantly increased the differentiation o ...[more]

PMID: 32836217

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Project description:Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4, and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome led to the rescue of DA neurons, when compared to transplantation of hBMSCs themselves, which can explain the recovery of secretome-injected animals' behavioral performance in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete important exosome-related molecules, such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.

Dataset Information

Synergistic effect of electric stimulation and mesenchymal stem cells against Parkinson's disease.

Publications

Synergistic effect of electric stimulation and mesenchymal stem cells against Parkinson's disease.

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