Chronic unpredictable stress influenced the behavioral but not the neurodegenerative impact of paraquat

Chris Rudyk,Zach Dwyer,Jessica Mcneill,Natalina Salmaso,Kyle Farmer,Natalie Prowse,Shawn Hayley

doi:10.1016/j.ynstr.2019.100179

Chris Rudyk, Zach Dwyer + Show 5 more

Open Access

https://doi.org/10.1016/j.ynstr.2019.100179

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Abstract

The impact of psychological stressors on the progression of motor and non-motor disturbances observed in Parkinson's disease (PD) has received little attention. Given that PD likely results from many different environmental “hits”, we were interested in whether a chronic unpredictable stressor regimen would act additively or possibly even synergistically to augment the impact of the toxicant, paraquat, which has previously been linked to PD. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering glucocorticoid receptor (GR) expression in the hippocampus. Furthermore, stressed mice that also received paraquat displayed synergistic motor coordination impairment on a rotarod test and augmented signs of anhedonia (sucrose preference test). The individual stressor and paraquat treatments also caused a range of non-motor (e.g. open field, Y and plus mazes) deficits, but there were no signs of an interaction (neither additive nor synergistic) between the insults. Similarly, paraquat caused the expected loss of substantia nigra dopamine neurons and microglial activation, but this effect was not further influenced by the chronic stressor. Taken together, these results indicate that paraquat has many effects comparable to that of a more traditional stressor and that at least some behavioral measures (i.e. sucrose preference and rotarod) are augmented by the combined pesticide and stress treatments. Thus, although psychological stressors might not necessarily increase the neurodegenerative effects of the toxicant exposure, they may promote co-morbid behaviors pathology.

Highlights

Characterized by the loss of dopamine neurons in the substantia nigra pars compacta (SNc), Parkinson's disease (PD) is the second most common neurodegenerative disease
Prior to saline or paraquat exposure, mice received three weeks of chronic unpredictable stress and were tested against non-stressed controls in order to verify the ability to the stressor regimen to induce anxiety and cognitive deficits
We report that our three weeks of stress did induce anxiety-like behavior as made evident in the elevated plus maze, wherein stressed mice spent less time in the open arms than nonstressed counterparts (t = 4.116, p < 0.01; Fig. 2 panel A)

Summary

Introduction

Characterized by the loss of dopamine neurons in the substantia nigra pars compacta (SNc), Parkinson's disease (PD) is the second most common neurodegenerative disease. Current evidence suggests that PD pathogenesis involves a complex interaction between a number of risk factors including genetic susceptibility, age, and environmental factors (i.e. exposure to psychological stress and/or exposure to chemical stressors like pesticides) that give rise to sporadic forms of the disease (Cannon and Greenamyre, 2013; Rappold et al, 2011). Paraquat is widely distributed throughout the brain including the olfactory bulbs, prefrontal cortex, and hippocampus where it can impart a variety of neurochemical changes that may in part explain some of these behavioral deficits (Peng et al, 2007; Prasad et al, 2009; Rappold et al, 2011)

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