Androgen-induced neuroplasticity in the hippocampus and cerebral cortex

雄激素增强认知功能，导致在许多脊椎动物中观察到的认知行为的正常性别差异。这些影响是如何发生的仍然未知。 我们已经证明，雄性激素给去势大鼠的海马和前额叶皮层（PFC）的神经元的顶端树突棘上的突触密度显着增加。由于大脑这些区域的棘突触密度增加与学习和记忆有关，我们假设这种作用可能代表类固醇对认知功能的积极作用机制的一部分。 雄激素和大脑之间相互作用的几个方面表明，类固醇对海马和PFC中突触神经支配的影响可能涉及新的细胞机制。我们建议，这些可能包括雄激素和神经递质系统之间的直接相互作用。 使用形态学，行为学和神经化学的方法相结合，我们建议探索雄激素诱导的突触可塑性的机制，以及雄激素的认知效应和海马和PFC的形态反应之间的时间和定量关系。不同剂量和时间的雄激素治疗过程的影响将被检查。 药理学技术和不同的天然和合成类固醇的效果的比较将被用来确定雄激素代谢的反应中的作用。最后，将测试的假设，即环境中的化学品暴露，在某些情况下，干扰雄激素的responses.The结果，从这些研究将提供一个更好的了解雄激素改变突触可塑性的机制，在涉及认知功能的大脑区域。对这些机制的进一步了解可能有助于理解认知行为的正常性别差异，与年龄相关的性腺激素分泌下降相关的认知变化，以及暴露于内分泌活性环境化学物质对认知功能的影响。

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.