title: MeHg Suppressed Neuronal Potency of Hippocampal NSCs Contributing to the Puberal Spatial Memory Deficits.
abstract: Hippocampal neurogenesis-related structural damage, particularly that leading to defective adult cognitive function, is considered an important risk factor for neurodegenerative and psychiatric diseases. Normal differentiation of neurons and glial cells during development is crucial in neurogenesis, which is particularly sensitive to the environmental toxicant methylmercury (MeHg). However, the exact effects of MeHg on hippocampal neural stem cell (hNSC) differentiation during puberty remain unknown. This study investigates whether MeHg exposure induces changes in hippocampal neurogenesis and whether these changes underlie cognitive defects in puberty. A rat model of methylmercury chloride (MeHgCl) exposure (0.4 mg/kg/day, PND 5-PND 33, 28 days) was established, and the Morris water maze was used to assess cognitive function. Primary hNSCs from hippocampal tissues of E16-day Sprague-Dawley rats were purified, identified, and cloned. hNSC proliferation and differentiation and the growth and morphology of newly generated neurons were observed by MTT and immunofluorescence assays. MeHg exposure induced defects in spatial learning and memory accompanied by a decrease in number of doublecortin (DCX)-positive cells in the dentate gyrus (DG). DCX is a surrogate marker for newly generated neurons. Proliferation and differentiation of hNSCs significantly decreased in the MeHg-treated groups. MeHg attenuated microtubule-associated protein-2 (MAP-2) expression in neurons and enhanced the glial fibrillary acidic protein (GFAP)-positive cell differentiation of hNSCs, thereby inducing degenerative changes in a dose-dependent manner. Moreover, MeHg induced deficits in hippocampus-dependent spatial learning and memory during adolescence as a consequence of decreased generation of DG neurons. Our findings suggested that MeHg exposure could be a potential risk factor for psychiatric and neurodegenerative diseases.
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China. tianjy2015@sina.cn.|Basic Medical School, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, China. tianjy2015@sina.cn.
authors.forename: Jianying
authors.initials: J
authors.lastname: Tian
authors.affiliation: The Research Center of Neurodegenerative Diseases and Aging, Medical College of Jinggangshan University, Ji'an, Jiangxi, 343000, China.
authors.forename: Yougen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Shengsen
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China.
authors.forename: Yuanye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China. yongyib@whu.edu.cn.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Bi
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology; D008767:Methylmercury Compounds / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D008767:Methylmercury Compounds; C004925:methylmercuric chloride
keywords: Hippocampal neurogenesis; Methylmercury; Neural stem cells; Proliferation and differentiation; Spatial learning and memory defect