Estradiol ameliorates the reduction in parvalbumin expression induced by ischemic brain injury.
Estradiol plays a neuroprotective role against focal cerebral ischemia. Parvalbumin is an intracellular Ca(2+)-binding protein. It exerts a neuroprotective effect against cytotoxic Ca(2+) overload. This study investigated whether estradiol modulates parvalbumin expression in focal cerebral ischemia and glutamate-induced neuronal cell death. Adult female rats were ovariectomied and treated with vehicle or estradiol prior to middle cerebral artery occlusion (MCAO). The cerebral cortex was collected 24h after MCAO. A proteomics approach showed a decrease of parvalbumin in MCAO-operated animals, while estradiol prevented the MCAO-induced decrease in parvalbumin. Reverse transcription-PCR and Western blot analyses confirmed that estradiol treatment attenuated the MCAO-induced decrease in parvalbumin levels. The results of immunohistochemical staining showed that the number of parvalbumin-positive cells decreased in MCAO-operated animals, and estradiol prevented the MCAO-induced decrease in parvalbumin-positive cells. In cultured hippocampal cells, glutamate exposure raised the intracellular Ca(2+) concentration, while estradiol treatment attenuated this increase. Moreover, estradiol prevented the decrease in parvalbumin induced by glutamate toxicity. These findings suggest that estradiol exerts a neuroprotective effect by preventing the MCAO-induced decrease of parvalbumin and by regulating intracellular Ca(2+) levels.
Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju 660-701, South Korea. Electronic address: pokoh@gsnu.ac.kr.
Phil-Ok
PO
Koh
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010052:Ovariectomy; D010320:Parvalbumins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D010320:Parvalbumins; D018698:Glutamic Acid; D004958:Estradiol; D002118:Calcium
Estradiol; Neuroprotection; Parvalbumin