Peripheral microcurrent stimulation improved motor behavior and preserved substantia nigra dopaminergic neurons in MPTP-treated mice, associated with reduced α-synuclein accumulation and downregulation of TLR4, PARP, and cleaved caspase-3.

This study presents a noninvasive, potentially translatable neuromodulation therapy that targets neuroinflammation and apoptotic pathways relevant to Parkinson's disease, offering a repurposable approach for neuroprotection that merits further validation in additional models and translational…

Parkinson's disease (PD) is a neurodegenerative disorder characterized by neuroinflammation and motor dysfunction. Current treatments primarily provide symptomatic relief. Microcurrent (MC) stimulation has recently emerged as a promising noninvasive technique for Alzheimer's disease; however, its therapeutic potential in PD remains underexplored. This study investigated the effects of MC therapy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Female C57BL/6 mice were divided into 3 groups: control, MPTP treated, and MPTP plus MC treated. A step-form waveform (5 V, 7 Hz base frequency with 44 kHz superposition) was applied for 4 weeks. Motor function was evaluated using rotarod and open field tests, and neuropathological changes were assessed by analyzing tyrosine hydroxylase, poly (ADP-ribose) polymerase (PARP), Toll-like receptor (TLR) proteins, caspase-3, and immunohistochemistry. MC therapy significantly improved motor activity in MPTP-treated mice, with increased latency to fall compared to the MPTP-only group. In the substantia nigra, the MC-treated mice had reduced tyrosine hydroxylase neuronal degradation and α-synuclein accumulation. Western blot analysis further revealed that the MC-treated mice had attenuated neuroinflammation by downregulating the TLR4 pathway and reducing PARP and cleaved caspase-3 expression. These findings suggest that MCs preserve dopaminergic neurons by suppressing neuroinflammation in a mouse model of PD, highlighting their potential as a therapeutic modality for PD.