AUTHOR=Torres-Rojas Carolina , Zhao Wenyuan , Zhuang Daming , O’Callaghan James P. , Lu Lu , Mulligan Megan K. , Williams Robert W. , Jones Byron C. 

TITLE=Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice

JOURNAL=Frontiers in Toxicology

VOLUME=3

YEAR=2021

URL=https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2021.722518

DOI=10.3389/ftox.2021.722518

ISSN=2673-3080

ABSTRACT=<p>Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) of six members of the BXD family of mice (<italic>n</italic> = 2–6 per strain). We injected males with 5 mg/kg paraquat weekly three times. The density of TH+ neurons counted by immunocytochemistry at 200x in eight or more sections through the SNc is reduced in five of the six strains relative to control (<italic>N</italic> = 4 ± 2 mice per strain). TH+ loss ranged from 0 to 20% with an SEM of 1%. The heritability was estimated using standard ANOVA and jackknife resampling and is 0.37 ± 0.05 in untreated animals and 0.47 ± 0.04 in treated animals. These results demonstrate genetic modulation and GxE variation in susceptibility to PQ exposure and the loss of TH staining in the substantia nigra.</p>