Lead exposure induced microgliosis and astrogliosis in hippocampus of young mice potentially by triggering TLR4-MyD88-NFκB signaling cascades
Lead exposure induced microgliosis and astrogliosis in hippocampus of young mice potentially by triggering TLR4-MyD88-NFκB signaling cascades
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铅暴露可能通过触发 TLR4-MyD88-NFkappaB 信号级联而诱导年轻小鼠海马中的小胶质细胞增生和星形胶质细胞增生。
DOI：
10.1016/j.toxlet.2015.09.015
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发表时间：
2015-12-03
影响因子：
3.5
通讯作者：
Chen, Liang-Wei
中科院分区：
文献类型：
--
作者：
Liu, Jin-Tao;Chen, Bei-Yu;Chen, Liang-Wei
海马中神经干细胞或祖细胞的正常增殖和分化对学习和记忆功能至关重要，而铅中毒可能会干扰学习和记忆功能，特别是在年轻人中。星形胶质细胞和小胶质细胞在调节海马神经发生中发挥重要作用，但其异常反应及其对海马神经发生的影响尚不清楚。因此，在本研究中，通过铅（铅，Pb）暴露的动物模型，在幼鼠海马中观察到包括小胶质细胞形成、星形胶质细胞形成和介导参与TLR4-MyD88-NF κ B信号级联的胶质反应。结果表明：(1)Pb暴露后海马小胶质细胞迅速活化；(2)同时检测到TLR4、MyD88、NF κ B表达水平升高；(3) Pb损伤组大鼠齿状回中可见brdu掺入祖细胞，且Pb损伤组大鼠齿状回中brdu掺入祖细胞数量显著增加；(4)海马中双皮质素标记的分化神经元无明显变化，但星形胶质细胞发生明显变化；(5)给予MyD88抑制肽可减弱或缓解上述效应；(6)海马组织中IL-1 β、TNF α、p38MAPK和ERK1/2表达水平升高，提示铅诱导的小胶质细胞增生和星形胶质细胞增生可能与炎症反应和MAPK信号激活有关。本研究总体数据表明，铅暴露可通过触发TLR4-MyD88-NF κ B信号级联触发或诱导幼龄小鼠海马异常小胶质细胞形成和星形胶质细胞形成，进而可能干扰海马神经发生和功能可塑性。(C) 2015年作者。爱思唯尔爱尔兰有限公司出版。
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-NF kappa B 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, NF kappa B 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-1 beta, TNF alpha, 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-NF kappa B signaling cascades, which might possibly thereafter disturb hippocampal neurogenesis and functional plasticity. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.