title: Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young adult rats.
abstract: Increasing epidemiological and toxicological evidence suggests that pesticides and other environmental exposures may be associated with the development of Parkinson's disease (PD). Chlorpyrifos (CPF) is a widely used organophosphorous pesticide with developmental neurotoxicity. Its neurotoxicity, notably on the monoamine system, suggests that exposure of CPF may induce dopaminergic neuronal injury. We investigated whether neonatal exposure to CPF contributes to initiation and progression of dopaminergic neurotoxicity and explored the possible underlying mechanisms. The newborn rats were administrated 5 mg/kg CPF subcutaneously from postnatal day (PND) 11 to PND 14 daily. The effect of CPF on dopaminergic neurons, microglia, astrocyte, nuclear factor-κB (NF-κB) p. 65 and p. 38 mitogen-activated protein kinase (MAPK) signaling pathways was analyzed in the substantia nigra of rats at 12h, 24h, 72 h, 16d and 46 d after exposure. CPF-treated rats exhibited significant reduction of dopaminergic neurons at 16d and 46 d after exposure, and a significant increase in the expression of microglia and astrocytes in the substantia nigra after CPF exposure. Intense activation of NF-κB p. 65 and p. 38 MAPK inflammatory signaling pathways was observed. Our findings indicate that neonatal exposure to CPF may induce long-term dopaminergic neuronal damage in the substantia nigra mediated by the activation of inflammatory response via NF-κB p. 65 and p. 38 MAPK pathways in the nigrostriatal system.
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Paediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Paediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Paediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, School of Medicine, Lexington, KY 40502, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.affiliation: Department of Paediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: llzhao2011@qq.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects; D015153:Blotting, Western; D002452:Cell Count; D004390:Chlorpyrifos / Q000633:toxicity*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects
chemical_list: D007306:Insecticides; D016328:NF-kappa B; D004390:Chlorpyrifos
keywords: Chlorpyrifos; Dopaminergic neuron; Inflammation; Mitogen-activated protein kinase; Nuclear factor-κB; Parkinson’s disease