Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos

Lein, Pamela J.; Bonner, Matthew R.; Farahat, Fayssal; Olson, James R.; Rohlman, Diane S.; Fenske, Richard A.; Lattal, K. Matthew; Lasarev, Michael; Galvin, Kit; Farahat, Taghreed M; Anger, W. Kent

doi:10.1016/j.neuro.2011.12.017

Cited by 27 publications

(17 citation statements)

References 37 publications

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“…In addition, most of them (77.5 %) sprayed pesticides only one time per month or less. The health effects of exposure to pesticides depends on the frequency and the concentration of pesticide use, as well as on the implementation of personal protective measures [25][26][27]. Therefore, our results suggest that farmers who had proper protective behavior had decreased exposure to the highly poisonous pesticides.…”

Section: Discussionmentioning

confidence: 69%

Health symptoms related to pesticide exposure and agricultural tasks among rice farmers from northern Thailand

Sapbamrer

Nata²

2013

Environ Health Prev Med

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Purpose The objective of this cross-sectional study was to investigate health symptoms related to occupational pesticide exposure and agricultural tasks in rice farmers. Methods Data on demographic variables and health symptoms associated with pesticide exposure were collected from 182 rice farmers (exposed subjects) and 122 non-farmers (controlled group) using interviews and measuring whole blood acetylcholinesterase (AChE) activity during August and October 2012. Results Rice farmers had a significantly lower median AChE activity than the controls (9,594 vs. 10,530 U/L, respectively) and a significantly higher prevalence of difficulty in breathing and chest pain [odds ratio (OR) 2.8, P \ 0.01 and OR 2.5, P \ 0.05, respectively]. The prevalence of dry throat and cramp was associated with those farmers who sprayed and mixed pesticides (OR 2.5 and 2.6 for dry throat, OR 2.5 and 2.9 for cramp, respectively; P \ 0.01). The prevalence of numbness and diarrhea was associated with those farmers who scattered seed (OR 2.2, P \ 0.01 and OR 3.6, P \ 0.05, respectively). The prevalence of numbness and increasing anxiety was also associated with those farmers who harvested crops (OR 3.6, P \ 0.01 and OR 3.0, P \ 0.05, respectively). Conclusions Our findings suggest that occupational pesticide exposure and agricultural tasks in the paddy field may be associated with the increasing prevalence of respiratory tract and muscle symptoms. This possibility warrants further investigation in more detail.

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Section: Discussionmentioning

confidence: 69%

Health symptoms related to pesticide exposure and agricultural tasks among rice farmers from northern Thailand

Sapbamrer

Nata²

2013

Environ Health Prev Med

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“…1 in Lee et al, 2015). An a priori power analysis indicated that 30 rats per treatment group were necessary for 80% power with an α of 0.05 based on the effect size presented in Lein et al (2012).…”

Section: Methodsmentioning

confidence: 99%

Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides

et al. 2016

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Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits), but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans (LE) rats were administered CPF at 3 or 10 mg/kg/d (s.c.) for 21 days. We quantified mRNA and non-coding RNA (ncRNA) expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58% or 13% of control levels in the hippocampus of rats in the 3 or 10 mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10 mg/kg/d dose group relative to controls. Of the 1382 differentially expressed genes identified by RNA-seq and microarray analysis, 67 were common to both approaches. Differential expression of six of these genes (Bdnf, Cort, Crhbp, Nptx2, Npy and Pnoc) was verified in an independent CPF exposure study; immunohistochemistry demonstrated that CRHBP and NPY were elevated in the CA1 region of the hippocampus at 10 mg/kg/d CPF. Gene ontology enrichment analysis suggested association of these genes with receptor-mediated cell survival signaling pathways. miR132/212 was also elevated in the CA1 hippocampal region, which may play a role in the disruption of neurotrophin-mediated cognitive processes after CPF administration. These findings identify potential mediators of CPF-induced neurobehavioral deficits following subchronic exposure to CPF at a level that inhibits hippocampal cholinesterase to less than 20% of control. An equally significant finding is that subchronic exposure to CPF at a level that produces more moderate inhibition of hippocampal cholinesterase (approximately 50% of control) does not produce a discernable change in gene expression.

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“…However, baseline AChE activity levels vary greatly, reductions in AChE activity do not correlate well with reported symptoms or observed deficits, manifestations of exposure persist long after ChE levels return to normal, and personal accounts of exposure may be incomplete (Rohlman et al, 2011, 2016). Fortunately, studies are currently underway to specifically expand the repertoire of biomarkers for OP exposure (Lein et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

et al. 2017

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Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

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Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos

Cited by 27 publications

References 37 publications

Health symptoms related to pesticide exposure and agricultural tasks among rice farmers from northern Thailand

Health symptoms related to pesticide exposure and agricultural tasks among rice farmers from northern Thailand

Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

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