Cholesterol induced calcium oscillation found in astrocytes

Abstract

Cholesterol is one of the most abundant molecules that constitutes the plasma membrane. The total cholesterol content in the brain is over 20%, and 50% of myelin is made up of cholesterol. In several neurodegenerative diseases, accumulation of free cholesterol in the extracellular space due to demyelination and neuronal death is suggested. However, the effect of free cholesterol in the brain parenchyma have not been focused. We found that cholesterol induces calcium oscillation in cultured astrocytes but not in neurons. The calcium oscillation lasted at least 4 hours. Removal of extracellular calcium decreased the oscillation frequency, but not totally blocked, while inhibitors against IP 3 receptor, calcium -ATPase and PLC blocked the calcium oscillation. Therefore, cholesterol induces calcium oscillation in astrocytes through the PLC-IP 3 pathway. Cholesterol treatment for 24 hours led cell death in neurons but not in astrocytes. The survival rate of astrocytes under cholesterol decreased when the calcium oscillation was suppressed. These results suggest that the calcium oscillation induced by cholesterol helps astrocytes to survive in high extracellular cholesterol condition, which may imply an astrocytic behavior under pathological conditions where extracellular cholesterol concentration is raised.