Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors
Dopamine regulates astrocytic IL-6 expression and process formation via dopamine receptors and adrenoceptors
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DOI：
10.1016/j.ejphar.2022.175110
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发表时间：
2022-08-05
影响因子：
5
通讯作者：
Otsuguro，Ken-ichi
中科院分区：
文献类型：
--
作者：
Morimoto，Kohei;Ouchi，Mai;Otsuguro，Ken-ichi
中枢神经系统中的多巴胺水平在诸如帕金森病、亨廷顿病和成瘾的病理条件下改变。在这些病理条件下，星形胶质细胞成为反应性星形胶质细胞，其特征在于形态学变化和参与发病机制的炎性细胞因子的释放。然而，多巴胺是否调节星形胶质细胞的形态和功能仍不清楚。阐明这些问题将有助于我们了解异常多巴胺信号引起的神经退行性疾病的发病机制。在这项研究中，我们研究了多巴胺对大鼠原代培养的星形胶质细胞和急性海马脑片中IL-6表达和突起形成的影响。多巴胺以浓度依赖性方式增加IL-6表达，并且伴有CREB磷酸化。低浓度多巴胺（1 μM）的作用被D1样受体拮抗剂抑制，而高浓度多巴胺（100 μM）的作用被β受体拮抗剂抑制，被D2样受体拮抗剂增强。此外，多巴胺（100 μM）促进突起形成，β-拮抗剂抑制，α-拮抗剂和D2样受体拮抗剂增强。在急性海马切片中，D1样受体激动剂和β-激动剂都改变了星形胶质细胞的形态。总之，这些结果表明多巴胺通过D1样受体和β-肾上腺素受体促进IL-6表达和过程形成。此外，还存在双向调节，即D1样受体和β受体的作用受到D2样受体和α2受体的负调节。
Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α2-adrenoceptors.