Mori Kohji, Ozaki Emi, Zhang Bo, Yang Lihua, Yokoyama Akiko, Takeda Ikuko, Maeda Nobuji, Sakanaka Masahiro, Tanaka Junya
Department of Physiology, School of Medicine, Ehime University, Shigenobu, Ehime 791-0295, Japan.
Neuropharmacology. 2002 Nov;43(6):1026-34. doi: 10.1016/s0028-3908(02)00211-3.
Microglial cells rapidly become activated in response to even minor damage of neurons, suggestive of the intimate interactions between neurons and microglial cells. Although mediators for microglia-neuron interactions have not been well identified, neurotransmitters are possible candidates transmitting signals from neurons to microglial cells. Among the neurotransmitters, we focused on the effects of norepinephrine and other adrenergic agonists on the functions of rat cultured microglial cells. Reverse transcriptase polymerase chain reaction studies revealed that microglial cells expressed mRNAs encoding alpha1A, alpha2A, beta1 and beta2 receptors. Norepinephrine and a beta2 adrenergic agonist terbutaline elevated intracellular cAMP level of microglial cells. Norepinephrine, an alpha1 agonist phenylephrine, a beta1 agonist dobutamine and terbutaline suppressed the expressions of mRNAs encoding pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor alpha. Release of tumor necrosis factor alpha and nitric oxide was suppressed by norepinephrine, phenylephrine, dobutamine and terbutaline. An alpha2 agonist clonidine and dobutamine upregulated the expression of mRNA encoding catechol-O-methyl transferase, an important enzyme to degrade norepinephrine. Norepinephrine, dobutamine and terbutaline upregulated the expressions of mRNA encoding 3-phospshoglycerate dehydrogenase, an essential enzyme for synthesis of L-serine and glycine, which are amino acids necessary for neuronal survival. Clonidine upregulated the expression of mRNA encoding an anti-apoptotic factor Bcl-xL. These results suggest that norepinephrine participates in the regulation of brain function at least partly by modulating the functions of microglia.
小胶质细胞对神经元的哪怕是轻微损伤都会迅速激活，这表明神经元与小胶质细胞之间存在密切的相互作用。尽管小胶质细胞与神经元相互作用的介质尚未完全明确，但神经递质可能是从神经元向小胶质细胞传递信号的候选者。在这些神经递质中，我们重点研究了去甲肾上腺素和其他肾上腺素能激动剂对大鼠培养小胶质细胞功能的影响。逆转录聚合酶链反应研究表明，小胶质细胞表达编码α1A、α2A、β1和β2受体的mRNA。去甲肾上腺素和β2肾上腺素能激动剂特布他林可提高小胶质细胞的细胞内cAMP水平。去甲肾上腺素、α1激动剂苯肾上腺素、β1激动剂多巴酚丁胺和特布他林可抑制编码促炎细胞因子白细胞介素-6和肿瘤坏死因子α的mRNA的表达。去甲肾上腺素、苯肾上腺素、多巴酚丁胺和特布他林可抑制肿瘤坏死因子α和一氧化氮的释放。α2激动剂可乐定和多巴酚丁胺上调了编码儿茶酚-O-甲基转移酶（一种降解去甲肾上腺素的重要酶）的mRNA的表达。去甲肾上腺素、多巴酚丁胺和特布他林上调了编码3-磷酸甘油酸脱氢酶（L-丝氨酸和甘氨酸合成所必需的酶，L-丝氨酸和甘氨酸是神经元存活所需的氨基酸）的mRNA的表达。可乐定上调了编码抗凋亡因子Bcl-xL的mRNA的表达。这些结果表明，去甲肾上腺素至少部分地通过调节小胶质细胞的功能参与脑功能的调节。
