Investigating the therapeutic potential of transcranial direct current stimulation in an experimental Parkinson’s model through glutamate pathway

The study’s objective was to look into the glutamate-mediated therapeutic effects of tDCS, which is known to modulate motor cortical plasticity and is thought to be a potential alternative treatment for Parkinson’s disease (PD), in 6-hydroxydopamine (6-OHDA) lesion rats with behavioral changes. Following tDCS application (0.5 mA anodal and cathodal tDCS, 30 min/day, 5 days/week, starting 7 days after the PD lesion) in PD animals, the effects of treatment on motor and non-motor behaviors as well as the glutamatergic pathway were determined. Four groups were conducted: Sham, PD, PD + A-tDCS (anodal stimulation) and PD + C-tDCS (cathodal stimulation). Apomorphine-induced rotation test, cylinder test, open field and new object recognition tests were performed. Glutamate, NMDA and EAAT2 levels were evaluated in the total hippocampus, prefrontal cortex and substantia nigra tissues. We found that tDCS treatment, regardless of anodal or cathodal, significantly attenuated 6-OHDA-induced motor activity deficits, as measured in open field test, apomorphine-induced rotations, and cylinder test performances, and was also effective in new object recognition memory. Glutamate and NMDA levels increased in the hippocampus, prefrontal cortex and substantia nigra tissues, while EAAT2 levels decreased in the PD group. tDCS application was significantly alleviated the effects of 6-OHDA. These results suggest that tDCS application can improve the aggravation of locomotor activity and learning performance, and exhibit neuroprotective effects through glutamate, NMDA and EAAT2 in PD rat model. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.