Iida Tomomitsu, Yanai Kazuhiko, Yoshikawa Takeo
Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Curr Top Behav Neurosci. 2022;59:241-259. doi: 10.1007/7854_2022_322.
Microglia, a category of glial cells in the central nervous system (CNS), have attracted much attention because of their important role in neuroinflammation. Many translational studies are currently ongoing to discover novel drugs targeting microglia for the treatment of various CNS disorders, such as Alzheimer's disease, Parkinson's disease (PD), and depression. Recent studies have shown that brain histamine, a neurotransmitter essential for the regulation of diverse brain functions, controls glial cells and neurons. In vitro studies using primary microglia and microglial cell lines have reported that histamine receptors are expressed in microglia and control microglial functions, including chemotaxis, migration, cytokine secretion, and autophagy. In vivo studies have demonstrated that histamine-related reagents could ameliorate abnormal symptoms in animal models of human diseases, such as amyotrophic lateral sclerosis (ALS), PD, and brain ischemia. Several human studies have revealed alterations in histamine receptor levels in ALS and PD, emphasizing the importance of the CNS histamine system, including histamine-dependent microglial modulation, as a therapeutic target for these disorders. In this review article, we summarize histamine-related research focusing on microglial functions.
小胶质细胞是中枢神经系统（CNS）中的一类神经胶质细胞，因其在神经炎症中的重要作用而备受关注。目前正在进行许多转化研究，以发现靶向小胶质细胞的新型药物，用于治疗各种中枢神经系统疾病，如阿尔茨海默病、帕金森病（PD）和抑郁症。最近的研究表明，脑组胺作为一种对多种脑功能调节至关重要的神经递质，可控制神经胶质细胞和神经元。使用原代小胶质细胞和小胶质细胞系的体外研究报告称，组胺受体在小胶质细胞中表达，并控制小胶质细胞的功能，包括趋化性、迁移、细胞因子分泌和自噬。体内研究表明，组胺相关试剂可改善人类疾病动物模型中的异常症状，如肌萎缩侧索硬化症（ALS）、帕金森病和脑缺血。几项人体研究揭示了肌萎缩侧索硬化症和帕金森病中组胺受体水平的变化，强调了中枢神经系统组胺系统（包括组胺依赖性小胶质细胞调节）作为这些疾病治疗靶点的重要性。在这篇综述文章中，我们总结了聚焦于小胶质细胞功能的组胺相关研究。
