STN-DBS exerts neuroprotection and anti-inflammatory effects in a Parkinson’s disease rat model

Abstract

Background Parkinson’s disease (PD) is a progressive neurodegeneration disease characterized by dopaminergic (DA) neuron loss, with chronic neuroinflammation. Subthalamic nucleus deep brain stimulation (STN-DBS) is clinically effective for the relief of parkinsonism motor symptoms. Here, we used a homemade device to investigate the effect of STN-DBS on neuroprotection and chronic neuroinflammation in a unilateral 6-hydroxydopamine (6-OHDA)-induced PD rat model. Method Male Sprague–Dawley rats received 6-OHDA injections into the striatum, followed by ipsilateral STN electrode implantation and high-frequency stimulation. Motor function was assessed by open-field and apomorphine-induced rotation tests. DA neuron survival, glial phenotype changes, and nuclear factor (NF)-κB pathway activity in the nigrostriatal system were evaluated using Western blotting, immunofluorescence, and RT-qPCR. Results STN-DBS improved motor deficits and decreased the loss of tyrosine hydroxylase-positive neurons. It promoted astrocytes presented a neuroprotective phenotype and increased expression of brain-derived neurotrophic factor, and microglia mainly presented an anti-inflammatory M2 phenotype instead of a pro-inflammatory M1 phenotype. These effects may be associated with IκB-α stabilization, the suppression of NF-κB hyperactivation, and the consequent reduction in the release of downstream pro-inflammatory cytokines. Conclusion Our findings highlight that our homemade device for STN-DBS is capable of inhibiting NF-κB, modulating glial phenotypes, mitigating neuroinflammation, and ultimately ameliorating parkinsonism deficits.