Abstract
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 (n = 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 (N = 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.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in progressive motor impairment resulting from selective loss of nigrostriatal dopamine neurons
Since PD affects the dopaminergic system and tyrosine hydroxylase (TH) is visualized in cell bodies, axons, and terminals in the dopaminergic system (Pickel et al, 1975), here we report the effects of PQ on TH-positive (TH+) neurons in the substantia nigra pars compacta (SNc) in BXD mouse strains
Even though exposures occur in the context of several risk factors, and the interaction between different chemicals and risk factors likely produces different outcomes, we are interested in uncovering the effect of paraquat on SNc neurons in a genetic reference population of mice
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in progressive motor impairment resulting from selective loss of nigrostriatal dopamine neurons. Sporadic PD is considered to be caused by some sort of environmental exposure (toxicants) combined with genetic susceptibility (Goldman et al, 2012). Of interest for our research, exposure to environmental toxicants, such as paraquat (PQ), has been associated with late-onset PD or sPD (Ritz et al, 2009). The cases of genetically linked PD are rare compared to sPD (Vila and Przedborski, 2004). Both types of PD share the common manifestation of motor impairment with the underlying accumulation of Lewy bodies and selective loss of nigrostriatal dopamine neurons as main pathophysiological features. We need a better understanding of the mechanism of toxicity of PQ relative to sPD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
