Internal Heat Acupuncture Treatment Inhibits Ferroptosis in the Spinal Dorsal Horn in Neurotoxin-Induced Parkinson's Disease Rats

Parkinson’s disease (PD) is the second neurodegenerative disorder with limited therapeutic options. Ferroptosis is involved in the pathogenesis of PD. This study aimed to investigate the neuroprotective effects of internal heat acupuncture (IHA) in a PD model, focusing on its impact on Ferroptosis. A neurotoxin-induced PD rat model was established using 6-hydroxydopamine (6-OHDA). These rats received IHA therapy. Behavioral tests were conducted to assess motor function and neuropathic pain. Serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Ferroptosis markers and the role of the GSK3β/Nrf2/GPX4 pathway were measured by western blot. The results showed that IHA enhanced motor function, attenuated pain hypersensitivity, and suppressed systemic inflammation in PD rats. Concurrently, IHA inhibited Ferroptosis in the spinal dorsal horn of PD rats, evidenced by decreased lipid peroxidation and iron accumulation, restored antioxidant capacity, and downregulated ferroptosis- and ferritinophagy-related markers. In addition, IHA decreased GSK3β expression and upregulated the Nrf2 and GPX4 expression, and overexpression of GSK3β reversed the effect on PD rats induced by IHA. In conclusion, IHA treatment suppresses Ferroptosis in the spinal dorsal horn by targeting the GSK3β/Nrf2/GPX4 pathway, thereby alleviating PD-induced motion disorders, neuropathic pain, and inflammation. These findings suggest that IHA may be an effective approach to treating PD and reveal a mechanism of its action.

Ferroptosis; GSK3β/Nrf2/GPX4 pathway; Internal heat acupuncture therapy; Parkinson's disease; Spinal dorsal horn.