Exposure of Zinc-induced Parkinson's disease-like non-motor and motor symptoms in relation to oxidative/nitrosative stress mediated neurodegeneration in the brain of Drosophila melanogaster

J Pharmacol Sci. 2025 Aug;158(4):303-309. doi: 10.1016/j.jphs.2025.05.010. Epub 2025 May 14.

Abstract

Parkinson's disease (PD) is the second most prevalent idiopathic neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to locomotor impairment. Despite extensive research, the etiology of PD remains unclear, and existing experimental models for pharmacological evaluation do not fully replicate the disease's hallmarks, necessitating the development of a cost-effective and reliable alternative. In recent past, Drosophila melanogaster has been utilized as a model organism for various neurodegenerative diseases, including PD. The present study was conceptualized to develop a reliable PD model in the Drosophila by Zinc (Zn+2).Chronic exposure to 20 mM Zn+2 for 7 days exhibited non-motor and motor PD-like symptoms in adult Drosophila flies, with reduced locomotory activity, indicating motor function deficit and reduced olfactory function and courtship behavior, indicating a deficit in non-motor function. These behavioral symptoms were associated with decreased dopamine levels. Furthermore, chronic Zn+2 exposure resulted in enhanced membrane lipid peroxidation and decreased endogenous antioxidants level in the Drosophila brain. These effects were primarily mediated by oxidative/nitrosative stress pathway. Thus, Zn2+-induced PD in Drosophila serves as a cost-effective model for drug discovery, facilitating the screening of potential therapeutic compounds. Additionally, this model offers a valuable platform to investigate the molecular mechanisms underlying PD pathophysiology.

Keywords: Drosophila melanogaster; Drug discovery; Olfactory function; Parkinson's disease; Pathophysiology; Zinc.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Behavior, Animal / drug effects
  • Brain* / metabolism
  • Brain* / pathology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons
  • Drosophila melanogaster
  • Lipid Peroxidation / drug effects
  • Motor Activity / drug effects
  • Nitrosative Stress* / drug effects
  • Oxidative Stress* / drug effects
  • Parkinson Disease* / etiology
  • Parkinson Disease* / physiopathology
  • Zinc* / toxicity

Substances

  • Zinc
  • Dopamine
  • Antioxidants