Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Glia. 2023 Sep;71(9):2071-2095. doi: 10.1002/glia.24390. Epub 2023 May 24.
Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting-edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous system (CNS) functions such as cognition, reward and feeding behavior in addition to their established contribution in brain diseases, pain, and CNS inflammation. Here, we discuss the latest insights in glial functions in health and disease that have been made through the application of chemogenetics. We will focus on the manipulation of intracellular signaling pathways induced by activation of the designer receptors exclusively activated by designer drugs (DREADDs) in astrocytes and microglia. We will also elaborate on some of the potential pitfalls and the translational potential of the DREADD technology.
在过去的十年中，人们对星形胶质细胞和小胶质细胞在正常和病态大脑功能中的作用有了深入的了解。最近，化学遗传工具已经成为一种前沿技术，可以对特定的神经胶质细胞类型进行靶向和时空精确的操作。因此，在星形胶质细胞和小胶质细胞功能方面取得了重大进展，表明胶质细胞如何干预中枢神经系统（CNS）功能，如认知、奖励和进食行为，除了它们在脑部疾病、疼痛和 CNS 炎症中的既定贡献。在这里，我们讨论了通过应用化学遗传学在健康和疾病中对神经胶质功能的最新见解。我们将重点讨论通过激活专门被设计药物激活的设计受体（DREADDs）在星形胶质细胞和小胶质细胞中诱导的细胞内信号通路的操作。我们还将详细阐述 DREADD 技术的一些潜在陷阱和转化潜力。
