Objective: The study aimed at deciphering status of redox genes in mid-brain regions of 2 major in vivo study models: mice/Drosophila melanogaster exposed to Parkinson toxins, which in turn would aid for finding efficient therapeutic targets. Additional objective was if there was pathophysiological variation across gender and age.

Background: One of the major etiology of Parkinsonian Motor disorder and neurodegeneration is oxidative stress and most of reports deal with commonly assessed antioxidant markers and their gene regulation like glutathione, superoxide dismutase etc. We set out to assess redox markers in neurons which are rarely estimated in experimental and clinical samples. This boosts understanding about detailed mechanism of how redox imbalance is so severe among dopaminergic neurons.

Method: Male and female mice of age groups 1, 12 and 20 months were exposed to complex I inhibitors-Rotenone(1mg/kg);Paraquat(20mg/kg) while untreated groups for each gender served as controls. Mice were monitored for phenotypic manifestation. 4mice from each group were euthanized on day7,21-post treatment and substantia nigra pars compact+striatal sections were assessed for degeneration while tissue homogenates were biochemically analyzed for gene expression patterns using RTPCR and activity of thioredoxin, thioredoxin reductase, GGL, GS, GR, HO-1.

In second paradigm-adult Drosophila (male;female separately, 3d, 10d, 30d old) were exposed to same toxins and monitored for neurobehavioural phenotype and terminally for biochemical/histopathological markers. Further Parkinsonian genes were assessed for their role in altering the expression patterns of redox genes using STRING;CHIMERA tools.

Results: There was a significant reduction in the expression patterns of Trx, TR, HO-1, GGL, GR, GS in male;female mice of age group 1;10 months while effect was not marked among 20month mice. Effect was similar among age;gender groups of flies. Activity levels matched expression pattern.

Conclusion: We strongly feel these rarely assessed redox markers could aid with early diagnosis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/consistent-downregulation-of-rarely-reported-antioxidant-genes-viz-ggl-tr-trx-ho-1-gr-gs-in-the-mid-brain-regions-among-mice-and-drosophila-exposed-to-parkinsonian-toxins-scope-as-early-diagn/