Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice.
Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice.
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DOI：
10.1016/j.neuro.2012.04.017
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发表时间：
2012-10
期刊：
影响因子：
3.4
通讯作者：
Lawrence DA
中科院分区：
文献类型：
--
作者：
Kasten-Jolly J;Pabello N;Bolivar VJ;Lawrence DA
铅（Pb）是最早发现的毒物之一，发育中的神经系统特别容易受到其毒性作用的影响。相对低的亚临床剂量的铅不会产生明显的脑病症状，但会影响认知、情绪和运动功能。本研究评估了发育期pb暴露对BALB/cAnNTac小鼠行为表现和基因表达的影响。幼鼠从妊娠第8天（gd）到出生后第21天（pnd）暴露于铅中，随后在成年后进行探索行为、旋转行走、莫里斯水迷宫和常驻入侵者试验。在探针试验中，铅暴露引起了探索行为和水迷宫性能的显著改变，但旋转杆性能没有受到影响。暴露于铅的雄鼠对笼子里的同伴表现出暴力行为，但对陌生人却没有。通过芯片和qRT-PCR对pnd21的基因表达进行了分析，以提供观察到的行为变化的分子联系。铅强烈上调丝裂原活化蛋白激酶（MAPKs）、细胞外基质受体（ECM）、局灶黏着和血管内皮生长因子（VEGF）信号通路中的基因表达，但下调糖结构-生物合成1、嘌呤代谢和n-聚糖生物合成通路中的基因表达。铅增加了主要组织相容性（MHC）蛋白、趋化因子Ccl28、趋化因子受体、IL-7、IL7R和蛋白酶的基因转录。qRT-PCR分析显示全脑caspase 1和NOS2基因表达增加。脑区IL-1β、caspase 1、NOS2、Trail、IL-18和IL-33基因表达分析表明，铅扰乱了促炎基因的区域间表达模式。抗炎细胞因子IL-10的脑区蛋白浓度仅在皮质区显著降低。结果表明，铅对雌雄小鼠行为的影响存在差异，雌性小鼠较少探索，雄性小鼠选择性地更具攻击性。基因表达数据指出了雌性和雄性老鼠大脑中神经炎症的证据。在雄性中，铅对与气味检测和社会行为相关的犁鼻受体基因表达的影响更大。
Lead (Pb) was one of the first poisons identified, and the developing nervous system is particularly vulnerable to its toxic effects. Relatively low, subclinical doses, of Pb that produce no overt signs of encephalopathy can affect cognitive, emotional, and motor functions. In the present study, the effects of developmental Pb-exposure on behavioral performance and gene expression in BALB/cAnNTac mice were evaluated. Pups were exposed to Pb from gestational-day (gd) 8 to postnatal-day (pnd) 21 and later evaluated in exploratory behavior, rotarod, Morris water maze, and resident-intruder assays as adults. Pb-exposure caused significant alterations in exploratory behavior and water maze performance during the probe trial, but rotarod performance was not affected. Pb-exposed males displayed violent behavior towards their cage mates, but not to a stranger in the resident-intruder assay. Gene expression analysis at pnd21 by microarray and qRT-PCR was performed to provide a molecular link to the behavior changes that were observed. Pb strongly up-regulated gene expression within the signaling pathways of mitogen activated protein kinases (MAPKs), extra-cellular matrix (ECM) receptor, focal adhesion, and vascular endothelial growth-factor (VEGF), but Pb down-regulated gene expression within the pathways for glycan structures-biosynthesis 1, purine metabolism, and N-glycan biosynthesis. Pb increased transcription of genes for major histocompatibility (MHC) proteins, the chemokine Ccl28, chemokine receptors, IL-7, IL7R, and proteases. The qRT-PCR analysis indicated an increase of gene expression in the whole brain for caspase 1 and NOS2. Analysis of IL-1β, caspase 1, NOS2, Trail, IL-18 and IL-33 gene expression of brain regions indicated that Pb perturbed the inter-regional expression pattern of pro-inflammatory genes. Brain region protein concentrations for IL-10, an anti-inflammatory cytokine, showed a significant decrease only within the cortex region. Results indicate that Pb differentially affects the behavior of male and female mice in that females did less exploration and the males were selectively more aggressive. Gene expression data pointed to evidence of neuroinflammation in the brain of both female and male mice. Pb had more of an effect in the males on expression of vomeronasal receptor genes associated with odor detection and social behavior.
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影响因子：
3.4
作者：
Brubaker CJ;Schmithorst VJ;Haynes EN;Dietrich KN;Egelhoff JC;Lindquist DM;Lanphear BP;Cecil KM
通讯作者：
Cecil KM
影响因子：
6.1
作者：
Barbeito AG;Martinez-Palma L;Vargas MR;Pehar M;Mañay N;Beckman JS;Barbeito L;Cassina P
通讯作者：
Cassina P
影响因子：
3.8
作者：
Bunn, TL;Parsons, PJ;Dietert, RR
通讯作者：
Dietert, RR
影响因子：
16.2
作者：
Datwani, Akash;McConnell, Michael J.;Kanold, Patrick O.;Micheva, Kristina D.;Busse, Brad;Shamloo, Mehrdad;Smith, Stephen J.;Shatz, Carla J.
通讯作者：
Shatz, Carla J.
影响因子：
2
作者：
Al-Saleh, Iman;Shinwari, Neptune;Rabah, Abdullah
通讯作者：
Rabah, Abdullah