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<p>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 <sup>64</sup>Zn and <sup>66</sup>Zn being the most abundant. Notably, healthy brain tissue is enriched in the lighter isotope <sup>64</sup>Zn, while heavier isotopes are hypothesized to accumulate with age. This study examined the therapeutic potential of intravenously administered isotopically enriched <sup>64</sup>Zn aspartate (<sup>64</sup>Zn-asp) in a rat model of PD induced by a single stereotactic intranigral injection of lipopolysaccharide (LPS, 10&#xa0;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 <sup>64</sup>Zn-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 <sup>64</sup>Zn-asp attenuates neuroinflammation and supports neuronal survival, indicating its potential as a candidate for disease-modifying strategies in PD.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Max Temnik,
  • Mariia Rudyk,
  • Alexandr Balakin,
  • Sergey Gurin,
  • Taisa Dovbynchuk,
  • Roman Byshovets,
  • Nataliia Dzubenko,
  • Ganna Tolstanova,
  • Larysa Skivka

摘要

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.

Graphical Abstract