Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Neuroscience. 2010 Sep 15;169(4):1567-74. doi: 10.1016/j.neuroscience.2010.06.023. Epub 2010 Jun 23.
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 vehicled once daily for 21 days. The expression of mGluR5 protein and mRNA was assessed by Western blotting and quantitative real-time PCR (qPCR). 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.
有几条证据表明，在重度抑郁症（MDD）中谷氨酸系统功能失调。最近，我们报道了 MDD 患者死后大脑中代谢型谷氨酸受体亚型 5（mGluR5）水平降低，但导致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）给药对大鼠额叶皮层和海马中 mGluR5 蛋白和 mRNA 表达的影响。大鼠每天皮下注射 CORT（40mg/kg）或 vehicle 一次，共 21 天。通过 Western blot 和定量实时 PCR（qPCR）评估 mGluR5 蛋白和 mRNA 的表达。此外，还在同一动物中测量了 mGluR1 蛋白。结果表明，尽管 CORT 处理大鼠海马中的 mGluR5 蛋白表达显著降低（-27%，P=0.0006），但 mRNA 水平不变。额叶皮层中的 mGluR5 mRNA 和蛋白水平以及两个脑区中的 mGluR1 蛋白水平也没有变化。我们的发现提供了第一个证据，表明慢性 CORT 暴露调节 mGluR5 的表达，与先前的尸检和影像学研究一致，这些研究表明 MDD 中 mGluR5 减少。我们的发现表明，皮质醇水平升高可能导致 MDD 中谷氨酸能神经传递受损。
