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Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period

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Abstract

Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.

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Acknowledgments

This work was supported by the Key National Scientific Foundation of China (#81230063); National Basic Research Program of China (973 Program, #2012CB525002); National Key Technology Support Program (#2014BAI12B04); National Scientific Foundation of China (#81302451, #81273101, #81472942, and #81402650); Program for Changjiang Scholars (T2011153) and Innovative Research Team in University (PCSIRT); and Shaanxi science and technology coordinating innovative project (2011KTCL03-19).

Conflict of Interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi’an, 710032, China

    Tao Wang, Rui-Li Guan, Ming-Chao Liu, Xue-Feng Shen, Jing Yuan Chen & Wen-Jing Luo

  2. Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi’an, Shaanxi Province, 710032, China

    Ming-Gao Zhao

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  1. Tao Wang
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Correspondence to Ming-Gao Zhao or Wen-Jing Luo.

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Wang, T., Guan, RL., Liu, MC. et al. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period. Mol Neurobiol 53, 3740–3752 (2016). https://doi.org/10.1007/s12035-015-9312-1

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