Differential long-term effects of developmental exposure to polychlorinated biphenyls 52, 138 or 180 on motor activity and neurotransmission. Gender dependence and mechanisms involved
Differential long-term effects of developmental exposure to polychlorinated biphenyls 52, 138 or 180 on motor activity and neurotransmission. Gender dependence and mechanisms involved
复制标题
DOI：
10.1016/j.neuint.2010.10.014
复制
发表时间：
2011-01-01
影响因子：
4.2
通讯作者：
Felipo, Vicente
中科院分区：
文献类型：
--
作者：
Boix, Jordi;Cauli, Omar;Felipo, Vicente
发育期暴露于多氯联苯（PCBs）可通过未知机制诱导人类运动功能改变。目前尚不清楚：（a）所有非二恶英类多氯联苯（NDL PCBs）都具有神经毒性或取决于氯化程度;（B）它们具有不同的神经毒性机制;（c）它们对男性和女性的影响不同。（2）多氯联苯（PCBs 52、138或180）对成年大鼠运动活动的影响不同;（3）对雄性或雌性的影响是否不同;（4）运动活动受损的机制。实验在大鼠4月龄时进行。多氯联苯52不影响运动活动，多氯联苯180降低男性运动活动，但不影响女性运动活动，多氯联苯138降低男性和女性运动活动。PCB 52或138不影响细胞外多巴胺在脑桥核（NAcc）。PCB 180在雄性和雌性中均使其增加。NAcc中的细胞外谷氨酸被三种PCBs减少。NAcc中代谢型谷氨酸受体（mGluRs）的激活增加了对照大鼠和暴露于PCB 52的大鼠的细胞外多巴胺，减少了暴露于PCB 180的大鼠的多巴胺。在暴露于PCB 138的大鼠中，mGluRs的激活增加了雌性大鼠的多巴胺，减少了雄性大鼠的多巴胺。mGluRs激活减少了对照大鼠和暴露于PCB 52的大鼠的细胞外谷氨酸，增加了暴露于PCB 180的大鼠的谷氨酸。在暴露于PCB 138的大鼠中，mGluRs的激活使雌性大鼠的谷氨酸减少，而使雄性大鼠的谷氨酸增加。在暴露于PCB 138或180的大鼠中，mGluRs激活后NAcc中谷氨酸释放增加将参与多巴胺释放减少和运动活动减少。(C)2010爱思唯尔有限公司保留所有权利。
Developmental exposure to polychlorinated biphenyls (PCBs) induces motor alterations in humans by unknown mechanisms. It remains unclear whether: (a) all non-dioxin-like (NDL) PCBs are neurotoxic or it depends on the grade of chlorination: (b) they have different neurotoxicity mechanisms: (c) they affect differently males and females.The aims of this work were to assess: (1) whether perinatal exposure to 3 NDL-PCBs with different grades of chlorination, (PCBs 52, 138 or 180) affects differentially motor activity in adult rats; (2) whether the effects are different in males or females and (3) the mechanisms involved in impaired motor activity.Rats were exposed to PCBs from gestational day 7 to post-natal day 21. Experiments were performed when the rats were 4 months-old. PCB52 did not affect motor activity, PCB180 reduced it in males but not in females and PCB138 reduced activity both in males and females. PCB52 or 138 did not affect extracellular dopamine in nucleus accumbens (NAcc). PCB180 increased it both in males and females. Extracellular glutamate in NAcc was reduced by the three PCBs.Activation of metabotropic glutamate receptors (mGluRs) in NAcc increased extracellular dopamine in control rats and in those exposed to PCB52 and reduced dopamine in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs increases dopamine in females and reduces it in males.The opposite changes were observed for glutamate. mGluRs activation reduced extracellular glutamate in control rats and in those exposed to PCB52 and increased glutamate in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs reduces glutamate in females and increases it in males.The data support that different NDL-PCBs affect differently motor activity. Increased glutamate release in NAcc following activation of mGluRs would be involved in reduced dopamine release and reduced motor activity in rats exposed to PCB138 or 180. (C) 2010 Elsevier Ltd. All rights reserved.