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MeHg Suppressed Neuronal Potency of Hippocampal NSCs Contributing to the Puberal Spatial Memory Deficits

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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.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (No. 81060231, 81160338, 30960110, 31360238) and Ningxia Universities Key Project (NGY2011039).

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Authors and Affiliations

  1. School of Public Health, Wuhan University, 115 Donghu Road, Wuchang District, Wuhan, Hubei, 430071, China

    Jianying Tian, Weiwei Chen, Shengsen Yang, Hao Wang, Jing Cui, Zhiyan Lu, Yuanye Lin & Yongyi Bi

  2. Basic Medical School, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, China

    Jianying Tian

  3. The Research Center of Neurodegenerative Diseases and Aging, Medical College of Jinggangshan University, Ji’an, Jiangxi, 343000, China

    Yougen Luo

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  1. Jianying Tian
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Correspondence to Jianying Tian or Yongyi Bi.

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All experiments were conducted in accordance with the rules of the National Committee on Care and Use of Experimental Animal Resources and approved by the Animal Ethics Committee of Ningxia Medical University.

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Tian, J., Luo, Y., Chen, W. et al. MeHg Suppressed Neuronal Potency of Hippocampal NSCs Contributing to the Puberal Spatial Memory Deficits. Biol Trace Elem Res 172, 424–436 (2016). https://doi.org/10.1007/s12011-015-0609-8

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