title: Lead exposure induced microgliosis and astrogliosis in hippocampus of young mice potentially by triggering TLR4-MyD88-NFκB signaling cascades.
abstract: Proper proliferation and differentiation of neural stem cells or progenitors in hippocampus is critical to learn and memory functions, which might be disturbed by lead toxicity particularly in young individuals. While astroglial and microglial cells are known to play an important role in regulating neurogenesis of hippocampus, their abnormal response and influence on hippocampal neurogenesis remains unclear. In this study, therefore, glial response including microgliosis, astrogliogenesis and mediating involvement of TLR4-MyD88-NFκB signaling cascades were observed in hippocampus of young mice by animal model with lead (plumbum, Pb) exposure. It revealed that (1) significant microglial activation occurred in hippocampus soon following Pb exposure; (2) increased levels of TLR4, MyD88, NFκB expression were concomitantly detected; (3) BrdU-incorporated progenitor cells were observed in dentate gyrus with significantly-increased numbers at d28 in Pb insult group; (4) obvious astrogliogenesis was observed while these doublecortin-labeled differentiated neurons were not significantly changed in hippocampus; (5) administration of MyD88 inhibitory peptide attenuated or relieved above effects; (6) enhanced expression levels of IL-1β, TNFα, p38MAPK and ERK1/2 were also detected in hippocampus, indicating potential implication of inflammatory response and MAPK signaling activation in lead-induced microgliosis and astrogliosis. Data of this study overall have indicated that lead exposure could trigger or induce abnormal microgliosis and astrogliogenesis in the hippocampus of young mice through triggering TLR4-MyD88-NFκB signaling cascades, which might possibly thereafter disturb hippocampal neurogenesis and functional plasticity.
authors.affiliation: Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China; Department of Neurosurgery, Tangdou Hospital, Fourth Military Medical University, China. Electronic address: jt_superliu@163.com.
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, China. Electronic address: chenby@fmmu.edu.cn.
authors.forename: Bei-Yu
authors.initials: BY
authors.lastname: Chen
authors.affiliation: Department of Occupational & Environmental Health, Fourth Military Medical University, China. Electronic address: zhangjieqiong1@163.com.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China. Electronic address: KuangF@fmmu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
authors.affiliation: Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China. Electronic address: chenlw@fmmu.edu.cn.
authors.forename: Liang-Wei
authors.initials: LW
authors.lastname: Chen
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001973:Bromodeoxyuridine; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007854:Lead / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D007854:Lead; D001973:Bromodeoxyuridine
keywords: Astrogliosis; Hippocampus; Lead toxicity; Microgliosis; Neurogenesis