Cholesterol-induced robust Ca oscillation in astrocytes required for survival and lipid droplet formation in high-cholesterol condition

Chihiro Adachi; Shio Otsuka; Takafumi Inoue

doi:10.1016/j.isci.2022.105138

Cholesterol-induced robust Ca oscillation in astrocytes required for survival and lipid droplet formation in high-cholesterol condition

iScience. 2022 Sep 16;25(10):105138. doi: 10.1016/j.isci.2022.105138. eCollection 2022 Oct 21.

Authors

Chihiro Adachi¹, Shio Otsuka¹, Takafumi Inoue¹

Affiliation

¹ Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.

Abstract

Cholesterol, one of the major cell membrane components, stabilizes membrane fluidity and regulates signal transduction. Beside its canonical roles, cholesterol has been reported to directly activate signaling pathways such as hedgehog (Hh). We recently found that astrocytes, one of the glial cells, respond to Hh pathway stimulation by Ca signaling. These notions led us to test if extracellularly applied cholesterol triggers Ca signaling in astrocytes. Here, we found that cholesterol application induces robust Ca oscillation only in astrocytes with different properties from the Hh-induced Ca response. The Ca oscillation has a long delay which corresponds to the onset of cholesterol accumulation in the plasma membrane. Blockade of the Ca oscillation resulted in enhancement of astrocytic cell death and disturbance of lipid droplet formation, implying a possibility that the cholesterol-induced Ca oscillation plays important roles in astrocytic survival and cholesterol handling under pathological conditions of cholesterol load such as demyelination.

Keywords: Biological sciences; Molecular neuroscience; Neuroscience.