Estradiol alleviates the ischemic brain injury-induced decrease of neuronal calcium sensor protein hippocalcin

•Estradiol plays a neuroprotective role against neuronal cell injury.•Estradiol prevents brain injury-induced decrease of in hippocalcin levels.•Estradiol attenuates the glutamate treatment-induced decrease in hippocalcin levels.

Estradiol has protective and reparative effects in neurodegenerative diseases. Hippocalcin is a neuronal calcium-sensor protein that acts as a calcium buffer to regulate the intracellular concentration of Ca2+. This study was investigated to elucidate whether estradiol regulates hippocalcin expression in a focal cerebral ischemia model and glutamate-treated neuronal cells. An ovariectomy was performed in adult female rats, and vehicle or estradiol was administered before middle cerebral artery occlusion (MCAO). Cerebral cortex tissues were collected at 24 h after MCAO. A proteomic approach revealed that hippocalcin expression decreased in vehicle-treated animals with combined MCAO, while estradiol treatment attenuated this decrease. Reverse transcription-PCR and Western blot analyses also showed that estradiol administration prevented the MCAO injury-induced decrease in hippocalcin expression. In cultured hippocampal cells, glutamate exposure increased the intracellular Ca2+ concentration, which was rescued by the presence of estradiol. Moreover, glutamate toxicity decreased hippocalcin expression, whereas estradiol attenuated this decrease. Together, these findings suggest that estradiol has a neuroprotective function by regulating hippocalcin expression and intracellular Ca2+ levels in ischemic brain injury.