Intravenous 64zn-Aspartate Mitigates Neuroinflammation and Motor Dysfunction in an Lps-Induced Parkinson’s Disease Rat Model

Emerging evidence links zinc dyshomeostasis to the pathogenesis of Parkinson's disease (PD), highlighting the need to explore zinc-based interventions. Zinc has five stable isotopes, with ⁶⁴Zn and ⁶⁶Zn being the most abundant. Notably, healthy brain tissue is enriched in the lighter isotope ⁶⁴Zn, while heavier isotopes are hypothesized to accumulate with age. This study examined the therapeutic potential of intravenously administered isotopically enriched ⁶⁴Zn aspartate (⁶⁴Zn-asp) in a rat model of PD induced by a single stereotactic intranigral injection of lipopolysaccharide (LPS, 10 μg), which simulates acute neuroinflammation followed by progressive neurodegeneration. Treatment effects were evaluated using behavioral assessments, immunological profiling, biochemical and molecular analyses, and histopathology. Rats treated with ⁶⁴Zn-asp showed a pronounced anti-inflammatory shift in microglial/macrophage metabolic profiles and reduced reactive astrogliosis. These changes were accompanied by improved motor performance and decreased anxiety-like behavior. Immunohistochemistry confirmed preservation of dopaminergic neurons. Overall, these findings suggest that ⁶⁴Zn-asp attenuates neuroinflammation and supports neuronal survival, indicating its potential as a candidate for disease-modifying strategies in PD.