Grant: Operating Grant

The hippocampus is a brain region that has continual neuronal birth throughout life, in all mammalian species studied to date, including the human. Women are more likely to suffer from Alzheimer's disease and depression than males, which may be linked to the levels of hormones in men and women. Estrogen, a mainly female hormone, enhances the production but potentially suppresses the survival of these new brain cells in the hippocampus of adult female, but not male, rodents. Testosterone, a mainly male hormone, enhances the survival of new brain cells in the hippocampus of male rodents, but it is not known how it affects female rodents. The proposed experiments are designed to investigate the effects of estrogen and testosterone on neuronal birth and survival in the hippocampus of adult male and female rodents. The objectives are: to determine the effects of repeated exposure to estradiol and testosterone on neuronal birth and survival; to determine the mechanisms of how estradiol and testosterone augment neuronal birth (how these hormones actually work to exert their effects on new cell growth in the brain); and finally to determine whether changes in new neuron survival by estrogen or testosterone affect learning and memory. We expect that estradiol will suppress new neuron survival by influencing their specific receptors. These findings will help determine how new neurons are produced in the adult brain and provide clues as to how estrogens and androgens exert their protective effects in patients with depression or Alzheimer's disease. The results of these experiments will elucidate the gender-specific mechanisms controlling the hormone-induced changes in neuronal birth which may ultimately lead to ways of inducing new brain cell growth to repair or replace lost cells in the gender-related diseases that have neuron loss.