Eun Su-Yong, Hong Yun Hwa, Kim Eun Hae, Jeon Hojeong, Suh Young Ho, Lee Ji Eun, Jo Chulman, Jo Sangmee Ahn, Kim Jun
Division of Brain Diseases, Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, Seoul 122-701, Republic of Korea.
Biochem Biophys Res Commun. 2004 Dec 3;325(1):320-7. doi: 10.1016/j.bbrc.2004.10.035.
It has been recently shown that the expression of various types of neurotransmitter receptors is not restricted to neurons but also observed in a majority of glial cells. However, their function in glial cells is not known well in both physiological and pathological conditions. Here, we investigated the role of glutamate receptor on c-fos gene expression in primary cultured and BV-2 microglia. Our results demonstrated that both c-fos mRNA and protein were dramatically induced following treatment with various glutamate receptor agonists (500muM); N-methyl-d-aspartic acid, kainic acid, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and (RS)-3,5-dihydroxyphenylglycine. The responses were significantly suppressed by specific antagonists and also by calcium chelating agents EGTA and BAPTA-AM. Our results suggest that glutamate receptor activation regulates c-fos gene expression by modifying intracellular calcium levels in microglia. These findings might provide an insight in to understanding the function of microglial glutamate receptors in neuron-to-glial interaction under the excitotoxic conditions.
最近研究表明，各种类型神经递质受体的表达不仅局限于神经元，在大多数胶质细胞中也可观察到。然而，在生理和病理条件下，它们在胶质细胞中的功能尚不清楚。在此，我们研究了谷氨酸受体对原代培养的小胶质细胞和BV-2小胶质细胞中c-fos基因表达的作用。我们的结果表明，在用各种谷氨酸受体激动剂（500μM）处理后，c-fos mRNA和蛋白均被显著诱导；这些激动剂包括N-甲基-D-天冬氨酸、海人酸、（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸和（RS）-3,5-二羟基苯甘氨酸。特异性拮抗剂以及钙螯合剂乙二醇双四乙酸（EGTA）和1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸-四乙酰甲酯（BAPTA-AM）可显著抑制这些反应。我们的结果表明，谷氨酸受体激活通过改变小胶质细胞内的钙水平来调节c-fos基因表达。这些发现可能有助于深入了解在兴奋性毒性条件下小胶质细胞谷氨酸受体在神经元与胶质细胞相互作用中的功能。
