Androgen-induced neuroplasticity in the hippocampus and cerebral cortex

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Androgens enhance cognitive function, contributing to the normal sex differences in cognitive behavior observed in many vertebrates. How these effects occur remains unknown.  We have demonstrated that administration of androgens to castrated rats markedly increases the density of synapses on the apical dendritic spines of neurons in the hippocampus and the prefrontal cortex (PFC). Since increased spine synapse density in these areas of the brain is associated with learning and memory, we hypothesize that this effect may represent part of the mechanism for the positive effects of the steroids on cognitive function.  Several aspects of the interaction between androgens and the brain suggest that the effects of the steroids on synaptic innervation in the hippocampus and PFC may involve novel cellular mechanisms. We propose that these may include direct interactions between androgens and neurotransmitter systems.  Using a combination of morphological, behavioral and neurochemical approaches, we propose to explore the mechanisms of androgen induced synaptic plasticity, as well as the temporal and quantitative relationships between the cognitive effects of androgen and the morphological responses of the hippocampus and PFC.  The effects of different doses and time courses of androgen treatment will be examined.  Pharmacological techniques and comparisons of the effects of different natural and synthetic steroids will be used to determine the role of androgen metabolism in the responses. Finally, the hypothesis will be tested that environmental chemical exposure may, under some circumstances, interfere with androgen responses.The results from these studies will provide an improved understanding of the mechanisms by which androgens alter synaptic plasticity, in regions of the brain involved in cognitive function. An improved knowledge of these mechanisms may help to understand normal sex differences in cognitive behavior, changes in cognition associated with age-related declines in gonadal hormone secretion, as well as the effects on cognitive function of exposure to endocrine-active environmental chemicals.