Institute for Physical Science and Technology, University of Maryland, College Park, MD, 20742, USA.
Institute of Organic Synthesis and Photoreactivity, National Research Council of Italy, 40129, Bologna, Italy.
Adv Biol (Weinh). 2023 Jun;7(6):e2200269. doi: 10.1002/adbi.202200269. Epub 2023 Jan 29.
Astrocytes are key regulators of brain homeostasis, equilibrating ion, water, and neurotransmitter concentrations and maintaining essential conditions for proper cognitive function. Recently, it has been shown that the excitability of the actin cytoskeleton manifests in second-scale dynamic fluctuations and acts as a sensor of chemophysical environmental cues. However, it is not known whether the cytoskeleton is excitable in astrocytes and how the homeostatic function of astrocytes is linked to the dynamics of the cytoskeleton. Here it is shown that homeostatic regulation involves the excitable dynamics of actin in certain subcellular regions of astrocytes, especially near the cell boundary. The results further indicate that actin dynamics concentrate into "hotspot" regions that selectively respond to certain chemophysical stimuli, specifically the homeostatic challenges of ion or water concentration increases. Substrate topography makes the actin dynamics of astrocytes weaker. Super-resolution images demonstrate that surface topography is also associated with the predominant perpendicular alignment of actin filaments near the cell boundary, whereas flat substrates result in an actin cortex mainly parallel to the cell boundary. Additionally, coculture with neurons increases both the probability of actin dynamics and the strength of hotspots. The excitable systems character of actin thus makes astrocytes direct participants in neural cell network dynamics.
星形胶质细胞是大脑内环境稳态的关键调节者，它们可以平衡离子、水和神经递质的浓度，并维持适当认知功能所必需的条件。最近的研究表明，肌动蛋白细胞骨架的兴奋性表现为二阶动态波动，并充当化学物理环境线索的传感器。然而，目前尚不清楚细胞骨架在星形胶质细胞中是否具有兴奋性，以及星形胶质细胞的内稳态功能如何与细胞骨架的动力学相关联。本文表明，内稳态调节涉及星形胶质细胞特定亚细胞区域中肌动蛋白的兴奋动力学，特别是在细胞边界附近。研究结果进一步表明，肌动蛋白动力学集中在“热点”区域，这些区域选择性地对某些化学物理刺激做出反应，特别是对离子或水浓度增加的内稳态挑战做出反应。基底拓扑结构使星形胶质细胞的肌动蛋白动力学减弱。超分辨率图像表明，表面拓扑结构也与细胞边界附近肌动蛋白丝的主要垂直排列有关，而平坦的基底则导致肌动蛋白皮质主要与细胞边界平行。此外，与神经元共培养会增加肌动蛋白动力学的概率和热点的强度。因此，肌动蛋白的兴奋系统特性使星形胶质细胞成为神经网络动力学的直接参与者。
