title: Involvement of microglia activation in the lead induced long-term potentiation impairment.
abstract: Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.
authors.affiliation: Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China.
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Liu
authors.forename: Xin-Qin
authors.initials: XQ
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Shen
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Che
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Chen
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D017628:Microglia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; D052247:Nitric Oxide Synthase Type II; D008911:Minocycline