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Neuroprotection by Progesterone Through Simulation of Mitochondrial Gene Expression

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Annual rept. 1 Aug 2001-31 Jul 2002

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In year 3 of this grant, we made more progress toward meeting our original objectives and have made progress on the additional objectives in our revised statements of work. The most important experimental results were as follows I Determined that low, physiological levels of plasma progesterone inhibited seizures produced by kainic acid while high levels of progesterone had no effect. 2. Protection against hippocampal neuronal death by progesterone is directly linked to inhibition of seizure activity. 3. Progesterone inhibition of kainate-induced seizures does not appear to be mediated via binding to its traditional nuclear receptor. 4. Low and high levels of plasma estrogen do not inhibit seizures produced by kainic acid. 5. Low and high levels of plasma estrogen inhibit hippocampal cell death caused by seizures induced by kainic acid. 6. Estrogen pretreatment, at supraphysiological levels, does not interfere with Ps seizure suppressive effects. 7. At low doses, estrogen attenuates seizure suppression by progesterone. 8. Mitochondrial gene expression is dependent upon mitochondrial mRNA stability, apparently controlled by a mitochondrial form of RNase L. 9. Mitochondrial Ca2 accumulation either inhibits or stimulates mitochondrial H2O2 production, depending on the respiratory substrate and the effect of Ca2 on the mitochondrial membrane potential. 10. Bax plus a BH3 domain peptide stimulate H2O2 production by brain mitochondria due to release of cytochrome c and this stimulation is insensitive to changes in membrane potential.

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  • Biochemistry
  • Medicine and Medical Research

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