title: Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway.
abstract: Chronic manganese exposure can produce cognitive deficits; however, the underlying mechanism remains unclear; reliable peripheral biomarker of Mn neurotoxicity have not yet been fully developed. Hence, this study aimed to investigate the mechanism of Mn-induced cognitive deficits and the potential biomarker of Mn neurotoxicity in rats. Thirty-two male Sprague Dawley rats were divided into four groups; these groups received intraperitoneal injections of 0, 5, 10 and 20 mg Mn/kg once daily, five days/week for 18 weeks. Learning and memory were assessed via Morris water maze test. Hippocampal and plasma Mn concentrations were measured through graphite furnace atomic absorption spectrometry. The levels of plasma BDNF, hippocampal BDNF, cAMP, protein kinase A, and pCREB were assessed through ELISA or Western blot. Results showed that the Mn concentrations in the hippocampus and plasma of the Mn-treated rats were higher than those of the control rats. Mn exposure impaired the learning and memory of rats. Plasma BDNF levels and hippocampal BDNF, cAMP, protein kinase A, and pCREB levels were significantly lower in the Mn-treated rats than in the control rats. Plasma BDNF levels were negatively correlated with the escape latency and the hippocampal and plasma Mn concentrations. By contrast, plasma BDNF levels were positively correlated with the number of platform crossings and the hippocampal cAMP and BDNF levels. Therefore, Mn impaired learning and memory probably by inhibiting the hippocampal cAMP signaling pathway in rats. Plasma BDNF levels may also be a potential effect biomarker of Mn neurotoxicity.
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Guiqiang
authors.initials: G
authors.lastname: Liang
authors.affiliation: Guangxi Center for Disease Prevention and Control, Nanning, Guangxi, PR China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Qin
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Li'e
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Ma
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Qing
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Guangxi Center for Disease Prevention and Control, Nanning, Guangxi, PR China.
authors.forename: Kangcheng
authors.initials: K
authors.lastname: Chen
authors.affiliation: Guangxi Center for Disease Prevention and Control, Nanning, Guangxi, PR China.
authors.forename: Yuman
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Nong
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China. Electronic address: yxbo21021@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Teaching and Research Section of Hygienic Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, PR China. Electronic address: email_zyf@163.com.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008345:Manganese / Q000097:blood / Q000378:metabolism; D020149:Manganese Poisoning / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D008345:Manganese; D000242:Cyclic AMP
keywords: BDNF; Cognitive deficits; Effect biomarker; Manganese; cAMP signaling pathway