Objective: The present study elucidated the neuroprotective effects of tDCS on the mitochondrial quality control pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model.

Background: Abnormal mitochondrial homeostasis is thought to be important for the pathogenesis of PD, and recent studies have demonstrated dysregulation of mitochondrial quality control, such as mitophagy and fission/fusion, in the brains of PD patients and in animal PD models. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, constitutes a promising approach for promoting recovery of various neurological conditions. However, little is known about its mechanism of action.

Method: We used the MPTP-induced neurotoxicity model, an in vivo model of PD. Mice were stimulated for 5 consecutive days with MPTP treatment. After observation of behavioral alteration using the rotarod test, mice were sacrificed for the measurement of the PD- and mitochondrial quality control-related protein levels in the substantia nigra.

Results: : tDCS improved the behavioral alterations and changes in tyrosine hydroxylase levels in MPTP-treated mice. Furthermore, tDCS attenuated mitochondrial damage, as indicated by diminished mitochondrial swelling and mitochondrial glutamate dehydrogenase activity in the MPTP-induced PD mouse model. MPTP significantly increased the level of mitophagy-related proteins, such as PTEN-induced putative kinase 1, Parkin, and microtubule-associated protein 1 light chain 3, and decreased the level of p62. These changes were attenuated by tDCS. MPTP also increased mitochondrial biogenesis-related proteins, including peroxisome proliferator-activated receptor-γ coactivator 1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, and tDCS decreased this increase. Furthermore, MPTP significantly increased fission-related protein dynamin-related protein 1 with no effect on fusion-related protein mitofusin-2, and tDCS attenuated these changes.

Conclusion: Our findings demonstrated the neuroprotective effect of anodal tDCS on the MPTP-induced neurotoxic mouse model through suppressing excessive mitophagy and balancing mitochondrial dynamics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/protective-effect-of-anodal-transcranial-direct-current-stimulation-on-1-methyl-4-phenyl-1236-tetrahydropyridine-mptp-induced-neurotoxicity-in-mice-via-modulating-mitochondrial-dynamics/