Paraquat and psychological stressor interactions as pertains to Parkinsonian co-morbidity

Abstract

A number of epidemiological and experimental studies have implicated the non-selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD). While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD). Hence, in the present study, we sought to take a multi-system approach to characterize the influence of paraquat upon extra-nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering neurochemical activity in the locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, dorsal striatum, and central amygdala. However, with the important exception striatal dopamine turnover, the stressor treatment did not further augment these effects. Additionally, paraquat altered inter-cytokine correlations and, to a lesser extent, circulating cytokine levels, and concomitant stress exposure modulated some of these effects. Finally, paraquat provoked significant (albeit modest) reductions of sucrose preference and weight gain, hinting at possible anhendonic-like or sickness responses. These data suggest that, in addition to being a well known oxidative stress generator, paraquat can act as a systemic stressor affecting hormonal and neurochemical activity, but largely not interacting with a concomitant stressor regimen.

Environmental toxicant exposure and Parkinson’s disease: LRRK2 and inflammatory processes

“…Consistent with our previous findings [141], paraquat acted as a systemic stressor, as evidenced by its elevation of plasma corticosterone and IL-6, provocation of sickness behavior and disturbances in nesting and motor behaviors. Indeed, we and others have shown that paraquat induced increased pro-inflammatory cytokine levels in the brain, as well as in the lungs and in serum [139,236,[344][345][346].…”

“…The present thesis experiments seek to investigate the pesticide, paraquat, either alone or in combination with the inflammatory endotoxin, LPS. Previous work in our laboratory has substantially explored these models, and found them to elicit highly reproducible PD-like behavioral and biological pathology [42,48,50,[139][140][141]. Meta-analyses and epidemiological studies primarily conducted on agricultural communities have demonstrated a strong link between pesticides and PD in humans [142][143][144].…”

Risk of lymphoma subtypes by occupational exposure in Southern Italy

“…Acute exposure to Paraquat accounted for several cases of fatal poisoning, while chronic exposure appears to be associated with respiratory disease and Parkinson’s disease [ 46 ]. Animal studies have shown DNA alterations in treated animals.…”

The role of pesticides in the etiology of lymphoma: A systematic review

“…Moreover, it was reported that the risk of NHL was increased in the users of paraquat which is a herbicide commonly used in agriculture [36]. Acute exposure to paraquat may lead to fatal poisoning, and chronic exposure may pave the way for respiratory diseases and Parkinson's disease [37]. In the study of Ferri et al, the result that exposure to captafol and paraquat was associated with the risk of lymphoma supports the literature on carcinogenic mechanism [23].…”