Neuroprotection by Progesterone through Stimulation of Mitochondrial Gene Expression

摘要

In year 2 of this grant, we have made more progress toward meeting our stated objectives. For Objective 1, we have; A. completed the studies establishing the dose and time course for progesterone in mediating neuroprotection against kainate-induced seizure and cell death. The studies showed that ovariectomized rats replaced with progesterone at physiological ranges reduced neuronal damage from seizures in proportion to the steroid's ability to reduce seizure activity. This activity is optimal at low to moderate progesterone dose. B. physiological levels of estrogen did not influence kainic acid seizures, but markedly reduced the neuronal damage that normally accompanies the seizures. C. have begun to study the interactions between estrogen and progesterone in influencing seizures and brain damage from persistent seizure activity, as well as investigating the mechanisms by which the steroids produce their effects. For Objectives 2 and 3, we have; obtained evidence that addition of progesterone (at concentrations of 5 and 10 MU) protects rat cerebellar neurons against glutamate-induced excitotoxic neuronal death. Addition of estradiol (1 MU) also protected rat cerebellar neurons against glutamate-induced excitotoxic neuronal death.