Cholesterol sulfate alters astrocyte metabolism and offers some neuroprotective effects

Introduction: Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and Dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as endogenous regulator of cholesterol synthesis. It is known that CS serves as a substrate for synthesizing other sterol sulfates in the brain. However, the role of CS in neurological insult and brain metabolism is unknown. Our goal in this study is to investigate the neuroprotective action of CS as well as its effect on brain energy metabolism. Materials and Methods: Primary astrocytes were prepared from the cortex of postnatal day 0-2 C57BL/6 pups and seeded in Dulbecco’s modified eagle medium (DMEM) with 10% FBS under normal glucose (5.5 mM). HT-22 cells were maintained in high glucose (25 mM) DMEM supplemented with charcoal stripped FBS. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte and HT-22 cells using Calcien AM cell viability assay, flow cytometry, seahorse extracellular flux analysis, and metabolism assay kits. Results: CS protects HT22 cells against glutamate toxicity and impact astrocyte metabolism by increasing ATP, and glycogen contents. Conclusion: Our study demonstrated that CS have neuroprotective effect and modulate brain energy metabolism. Further studies are needed to determine the mechanisms underlying the neuroprotective action of CS and its action on brain energy metabolism.