کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6262938 | 1613817 | 2015 | 12 صفحه PDF | دانلود رایگان |
- DHEA restores memory deficits following BCCAO ischemia via Ï1 receptor stimulation.
- Reduced CaMKII and ERK activities in the hippocampus are improved by DHEA treatment.
- DHEA rescues the decreases in ATP and Ï1 receptor levels following BCCAO ischemia.
Dehydroepiandrosterone (DHEA) is the most abundant neurosteroid synthesized de novo in the central nervous system. Oral DHEA administration elicits neuroprotection and cognitive improvement, but mechanisms underlying these functions in cerebral ischemia have remained unclear. Since DHEA is the endogenous ligand for the sigma-1 receptor (Ï1R), we determined whether oral DHEA administration prevents neuronal cell death and improves cognition via Ï1R stimulation in brain ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. Twenty-four hours after BCCAO ischemia, mice were administered DHEA (15 or 30 mg/kg p.o.) daily for 11 consecutive days. Memory deficits following brain ischemia were improved by DHEA administration dose-dependently. Accordingly, DHEA administration significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice. Interestingly, DHEA administration rescued decreases in Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in the CA1 region. Moreover, DHEA administration significantly ameliorated decreases in adenosine 5ʹ-triphosphate (ATP) levels and decreased Ï1R expression levels in CA1 following BCCAO ischemia. Finally, co-treatment of mice with the Ï1R antagonist NE-100 (1 mg/kg, p.o.) blocked DHEA effects on memory improvement and neuroprotection in ischemic mice. Taken together, DHEA prevents neuronal cell death and activates CaMKII via Ï1R stimulation, thereby improving cognitive deficits following brain ischemia.
Journal: Brain Research - Volume 1622, 5 October 2015, Pages 102-113