title: Alterations of Synaptic Proteins in the Hippocampus of Mouse Offspring Induced by Developmental Lead Exposure.
abstract: Lead exposure can cause cognitive dysfunction in children, thus it still raises important public health concerns in China and other countries. However, the underlying molecular mechanisms are still not well defined. In this study, we aimed to elucidate the mechanisms underlying lead neurotoxicity by focusing on alterations of synaptic proteins in the mouse hippocampus at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0, and 2.0 g/L lead via drinking water from the first day of gestation until postnatal day (PND) 40. Synaptic ultrastructure and expressions of postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS) and synaptophysin (SYP) at both protein and gene levels in the hippocampus were analyzed. The results revealed that developmental lead exposure caused a diminished postsynaptic density in the hippocampus. Moreover, the protein levels of PSD-95, nNOS, and SYP decreased significantly due to developmental lead exposure. On the other hand, the messenger RNA (mRNA) levels of PSD-95 and SYP decreased significantly in PND 40 mice exposed to lead. Collectively, developmental lead exposure might result in decreased protein and gene expressions of both presynaptic and postsynaptic proteins. Our findings raised a possibility that alterations of synaptic proteins in the hippocampus induced by lead exposure at the early life might serve an important role for the subsequent intellectual impairments, e.g., deficits in spatial learning and memory ability at later ages shown in our recently published paper.
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Physiology, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
authors.forename: Fenghong
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China. jinyp@mail.cmu.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D007854:Lead / Q000633:toxicity*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007854:Lead; D052248:Nitric Oxide Synthase Type I
keywords: Developmental lead exposure; Mice; Neuronal nitric oxide synthase (nNOS); Postsynaptic density protein-95 (PSD-95); Synaptic proteins; Synaptophysin (SYP)