title: The effect of HMGB1 on sub-toxic chlorpyrifos exposure-induced neuroinflammation in amygdala of neonatal rats.
abstract: Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5mg/kg CPF for 4 consecutive days (postnatal day 11-14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala.
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Mengwen
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cardiology Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, School of Medicine, Lexington, KY, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. Electronic address: llzhao2011@qq.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D004390:Chlorpyrifos / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D021381:Protein Transport; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D016328:NF-kappa B; D010575:Pesticides; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D019695:Glycyrrhizic Acid; D004390:Chlorpyrifos
keywords: Chlorpyrifos; High-mobility group box 1; Inflammatory; Interleukin-6; Nuclear factor kappa B; Tumor necrosis factor-α