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Postnatal zinc or paraquat administration increases paraquat or zinc-induced loss of dopaminergic neurons: insight into augmented neurodegeneration

Abstract

Epidemiological evidences have shown an association of exposure to pesticides or heavy metals with increased incidences of Parkinson’s disease (PD) in humans. Exposure to pesticides or metals during the decisive period of the brain development increases the susceptibility of dopaminergic neurons upon re-exposure in adult rodents. However, the effect of early life exposure to pesticide on the heavy metal-induced neurodegeneration or heavy metal on pesticide-induced neurodegeneration is not yet explored. The current study explored the effect of developmental exposure to zinc (Zn), a metal or paraquat (PQ), a pesticide on the nigrostriatal dopaminergic neurons of rats challenged to Zn or PQ during adulthood. Exposure of Zn or PQ during adulthood alone exhibited marked reduction in motor activities, striatal dopamine and metabolites, glutathione content and number of dopaminergic neurons. However, the levels of lipid peroxidation, protein carbonyls, superoxide dismutase activity, pro-inflammatory cytokines and 4-hydroxynonenal-protein adducts were increased. While the expression of vesicular monoamine transporter-2 and tyrosine hydroxylase were attenuated, dopamine transporter and microglial marker Iba-1 expression, activated microglia, nuclear factor-kappa B activation, mitochondrial cytochrome c release and caspase-3/9 activation were augmented following Zn or PQ exposure. Albeit postnatal alone exposure did not alter any of the studied parameters, the developmental administration of Zn/PQ in re-challenged adult rats produced more pronounced changes in the aforementioned variables as compared with adulthood Zn or PQ alone intoxicated animals. The results demonstrate that postnatal Zn/PQ intoxication dents the oxidative stress, inflammation, cell death and dopamine metabolism and storage regulating machineries, which speed up the toxicant-induced degeneration during adulthood.

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Acknowledgements

The research fellowships offered to Namrata Mittra and Garima Singh by the Department of Science & Technology (DST), New Delhi, India and Amit Kumar Chauhan by the Council for Scientific and Industrial Research (CSIR), New Delhi, India are sincerely acknowledged. The authors also appreciate the financial support provided by the CSIR to Chetna Singh through CSIR-network program ‘Integrated NextGen Approaches in Health, Disease and Environmental Toxicity’ [INDEPTH (BSC-0111)]. The CSIR-IITR communication number assigned to the article is 3595.

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Correspondence to Chetna Singh.

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The study was carried out in compliance with the guidelines of the committee for the purpose of control and supervision of experiments on animals (CPCSEA) after the approval by Institutional Animal Ethics Committee.

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Mittra, N., Chauhan, A.K., Singh, G. et al. Postnatal zinc or paraquat administration increases paraquat or zinc-induced loss of dopaminergic neurons: insight into augmented neurodegeneration. Mol Cell Biochem (2020). https://doi.org/10.1007/s11010-020-03694-x

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Keywords

  • Zinc
  • Paraquat
  • Neurodegeneration
  • Oxidative stress
  • Inflammation