Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex
Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex
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DOI：
10.1016/j.neuropharm.2007.05.019
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Cuomo, Vincenzo
中科院分区：
文献类型：
--
作者：
Castaldo, Pasqualina;Magi, Simona;Cuomo, Vincenzo
产前暴露于CBI受体激动剂（R）-（+）-[2，3-二氢-5-甲基-3-（4-吗啉基甲基）-吡咯并[1，2，3-de]-1，4-苯并恶嗪基]-（1-萘基）甲酮）甲磺酸盐（WIN），每日剂量为0.5 mg/kg，和δ 9-四氢大麻酚（δ（9）-THC），每日剂量为5 mg/kg，相对于那些在载体处理的母体前出生的后代，青少年后代（40日龄）的额叶大脑皮层中的透析液谷氨酸水平降低。WIN治疗诱导的V-max L-[H-3]谷氨酸摄取的统计学显着增强，而它没有修改谷氨酸Km，在青春期大鼠的额叶大脑皮层突触体。Western印迹分析，无论是在膜蛋白来源于匀浆和额叶大脑皮层突触体提取的蛋白质，显示产前WIN曝光增强谷氨酸转运蛋白1（GLT 1）和兴奋性氨基酸载体1（EAAC 1）的表达。此外，额叶皮质区的免疫细胞化学分析显示，更强烈的GLT 1和EAAC 1免疫反应（ir）分布在WIN-treated组。总的来说，这些结果表明，产前暴露于大麻素CB 1受体激动剂WIN增加GLT 1和EAAC 1谷氨酸转运蛋白（GluTs）的表达和功能活性相关的皮质谷氨酸外流减少，在青春期大鼠。这些发现可能有助于解释在怀孕期间使用大麻的母亲的后代中观察到的认知障碍的机制。(C)2007爱思唯尔有限公司保留所有权利。
Prenatal exposure to the CBI receptoragonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta 9-tetrahydrocannabinol (Delta(9)-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born front vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of V-max L-[H-3]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC 1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 receptor agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy. (C) 2007 Elsevier Ltd. All rights reserved.