Developmental exposure to pesticides zineb and/or endosulfan renders the nigrostriatal dopamine system more susceptible to these environmental chemicals later in life.
Several epidemiological studies have suggested a role for environmental pesticide exposures in idiopathic Parkinson's disease. The purpose of this study was to test the hypothesis that exposure to pesticides such as endosulfan and/or zineb during critical periods of postnatal development could result in neuronal dysfunction and enhance the impact of these pesticides during exposure as adults. C57BL/6 mice, exposed daily to each of the pesticides or their mixtures from postnatal days 5 to 19, exhibited insignificant changes in striatal dopamine, acetylcholinesterase and alpha-synuclein levels. However, mice exposed to these pesticides as juveniles and re-exposed at 8 months of age had significantly altered striatum and brain cortex neurotransmitter levels. Thus, mice re-exposed during adulthood to zineb, endosulfan and their mixtures showed a significantly depleted striatal dopamine levels, to 22, 16 and 35% of control, respectively. Acetylcholinesterase activity in the cerebral cortex was significantly increased in all pesticide treated groups (rho< or =0.05) upon repeated exposure, and pesticide mixture treatment also significantly increased levels of normal and aggregated alpha-synuclein. Collectively, these findings support our hypothesis that exposure to pesticides such as endosulfan and zineb during critical periods of postnatal development contributes to neurotransmitter changes upon re-challenge in adulthood.
Jia
Zhenquan
Z
Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Misra
Hara P
HP
D000110:Acetylcholinesterase / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D004726:Endosulfan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010575:Pesticides / Q000494:pharmacology*; D051843:Synucleins / Q000378:metabolism; D015038:Zineb / Q000494:pharmacology*
D010575:Pesticides; D051843:Synucleins; D000110:Acetylcholinesterase; D004726:Endosulfan; D004298:Dopamine; D015038:Zineb