Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

摘要

BackgroundHigh concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca²⁺) and generation of free radicals such as peroxynitrite (ONOO^-). Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca²⁺ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA) receptor and nitric oxide synthase (NOS) along with the effect of 17β-estradiol (17β-E2) and a more potent antioxidant Δ⁸, 17β-estradiol (Δ⁸, 17β-E2) on cell viability and intracellular Ca²⁺ ([Ca²⁺]i), following treatment of rat cortical cells with glutamate, was investigated.