Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus.
Chronic corticosterone administration down-regulates metabotropic glutamate receptor 5 protein expression in the rat hippocampus.
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DOI：
10.1016/j.neuroscience.2010.06.023
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发表时间：
2010-09-15
期刊：
影响因子：
3.3
通讯作者：
Karolewicz, B.
中科院分区：
文献类型：
--
作者：
Iyo, A. H.;Feyissa, A. M.;Chandran, A.;Austin, M. C.;Regunathan, S.;Karolewicz, B.
关键词：
几条证据表明，在重度抑郁症（MDD）谷氨酸系统功能失调。最近，我们报道了代谢型谷氨酸受体亚型5（mGluR 5）在MDD死后的大脑中的水平降低，但诱导这些异常的神经生物学机制尚不清楚。在本研究中，我们研究了慢性皮质酮（CORT）给药对大鼠额叶皮质和海马mGluR 5蛋白和mRNA表达的影响。大鼠皮下注射CORT（40 mg/kg，s.c.）或载体，每天一次，持续21天。Western blotting和实时荧光定量PCR检测mGluR 5蛋白和mRNA的表达。此外，在相同动物中测量mGluR 1蛋白。结果显示，虽然CORT处理大鼠海马中mGluR 5蛋白表达显著降低（-27%，p=0.0006），但mRNA水平无变化。额叶皮层中的mGluR 5 mRNA和蛋白水平以及两个大脑区域中的mGluR 1蛋白水平也没有变化。我们的研究结果提供了第一个证据表明，慢性CORT暴露调节mGluR 5的表达，并与先前的尸检和成像研究显示MDD中mGluR 5减少。我们的研究结果表明，糖皮质激素水平升高可能有助于损害谷氨酸神经传递在MDD。
Several lines of evidence suggest a dysfunctional glutamate system in major depressive disorder (MDD). Recently, we reported reduced levels of metabotropic glutamate receptor subtype 5 (mGluR5) in postmortem brains in MDD, however the neurobiological mechanisms that induce these abnormalities are unclear. In the present study, we examined the effect of chronic corticosterone (CORT) administration on the expression of mGluR5 protein and mRNA in the rat frontal cortex and hippocampus. Rats were injected with CORT (40 mg/kg, s.c.) or vehicle once daily for 21 days. The expression of mGluR5 protein and mRNA was assessed by Western blotting and quantitative real-time PCR. In addition, mGluR1 protein was measured in the same animals. The results revealed that while there was a significant reduction (− 27 %, p=0.0006) in mGluR5 protein expression in the hippocampus from CORT treated rats, mRNA levels were unchanged. Also unchanged were mGluR5 mRNA and protein levels in the frontal cortex and mGluR1 protein levels in both brain regions. Our findings provide the first evidence that chronic CORT exposure regulates the expression of mGluR5 and are in line with previous postmortem and imaging studies showing reduced mGluR5 in MDD. Our findings suggest that elevated levels of glucocorticoids may contribute to impairments in glutamate neurotransmission in MDD.
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影响因子：
5
作者：
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