title: Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.
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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Rui-Li
authors.initials: RL
authors.lastname: Guan
authors.affiliation: 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.
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Jing Yuan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China. minggao@fmmu.edu.cn.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.affiliation: 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. luowenj@fmmu.edu.cn.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Luo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000187:drug effects; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007854:Lead / Q000633:toxicity*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D018698:Glutamic Acid
keywords: Dendritic spine; Fear-conditioned memory; Hippocampus; Lead (Pb); Synaptic plasiticity