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

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Neurobiol Stress. 2019 Nov; 11: 100179.

Neurobiology of Stress neurons and microglial activation, but this effect was not
Elsevier further influenced by the chronic stressor. Taken
together, these results indicate that paraquat has many
Chronic unpredictable stress effects comparable to that of a more traditional stressor

influenced the behavioral but not the and that at least some behavioral measures (i.e. sucrose

neurodegenerative impact of paraquat preference and rotarod) are augmented by the combined
pesticide and stress treatments. Thus, although
Chris Rudyk, Zach Dwyer, [...], and Shawn Hayley psychological stressors might not necessarily increase
the neurodegenerative effects of the toxicant exposure,
Additional article information
they may promote co-morbid behaviors pathology.

Abstract Keywords: Parkinson's, Stress, Inflammatory, Microglia,


Cytokine, Toxicity
The impact of psychological stressors on the progression
Abbreviations: AAR, alternate arm return; ANOVA,
of motor and non-motor disturbances observed in
analysis of variance; BCA, bicinchoninic acid; BDNF,
Parkinson's disease (PD) has received little attention.
brain derived neurotrophic factor; CUS, chronic
Given that PD likely results from many different
unpredictable stress; EDTA, ethylenediaminetetraacetic
environmental “hits”, we were interested in whether a
acid; ELISA, enzyme-linked immunosorbent assay;
chronic unpredictable stressor regimen would act
EPM, elevated plus maze; FST, forced swim test; GR,
additively or possibly even synergistically to augment
glucocorticoid receptor; HPA, hypothalamus-pituitary
the impact of the toxicant, paraquat, which has
adrenal; IBA1, ionized calcium-binding adapter
previously been linked to PD. Our findings support the
molecule 1; MMx, Micromax; PB, phosphate buffer;
contention that paraquat itself acted as a systemic
PBS, phosphate buffered saline; PD, Parkinson's disease;
stressor, with the pesticide increasing plasma
PFA, paraformaldehyde; pGR, phosphate glucocorticoid
corticosterone, as well as altering glucocorticoid
receptor; PVDF, polyvinylidene difluoride; RIPA, Radio
receptor (GR) expression in the hippocampus.
Immuno Precipitation Assay; RR, rotarod; SAB,
Furthermore, stressed mice that also received paraquat
spontaneous alternation behavior; SAR, same arm
displayed synergistic motor coordination impairment on
return; SDS, sodium dodecyl sulphate; SNc, substantia
a rotarod test and augmented signs of anhedonia
nigra pars compacta; SPT, sucrose preference test; TH,
(sucrose preference test). The individual stressor and
tyrosine hydroxylase; VTA, ventral tegmental area
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 1. Introduction
synergistic) between the insults. Similarly, paraquat Primarily characterized by the loss of dopamine neurons
caused the expected loss of substantia nigra dopamine in the substantia nigra pars compacta (SNc), Parkinson's

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