Protective effects of repetitive transcranial magnetic stimulation against 6-OHDA-induced Parkinson's symptoms in a mice model: the key role of miR-409-3p/PDHB axis

Abstract

Aim: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique showing improvement effects on Parkinson's disease (PD). Multiple microRNAs (miRs) are dys-expressed during the progression of PD. In the current study, the potential involvement of miRs in the anti-PD effects of rTMS was explored.

Methods: PD symptoms were induced in mice with 6-OHDA. The expression profile of miRs influenced by rTMS in PD mice was detected by microarray technique and validated by RT-qPCR detection. The PD mice were treated with rTMS and the changes in cognitive behaviors, substantia nigra neuron number, brain histology, and Aβ_1-42 level were detected. The activity of miR-409-3p/PDHB axis was also detected to preliminarily explain the interaction between miRs and rTMS.

Results: The detection of microarray showed that 266 miRs were dys-expressed in PD mice after the administration of rTMS, including 101 up-regulated ones and 146 down-regulated ones. With validation by RT-qPCR detection, miR-409-3p was selected for subsequent assays. Administrations of rTMS improved cognitive behaviors of mice, increased neuron number, and attenuated brain injuries induced by 6-OHDA. The cerebrospinal fluid (CSF) level of Aβ_1-42 was induced, while the brain level of Aβ_1-42 was suppressed by rTMS. Regarding miR-409-3p/PDHB axis, rTMS administrations suppressed miR-409-3p level and increased the expression of PDHB.

Conclusion: Administrations of rTMS showed considerable protective effects on brain tissues against PD-induced injuries, which was associated with the changes in miR levels. The current study demonstrated that the inhibition of miR-409-3p by rTMS contributed to the attenuation of PD by inducing PDHB.