Estrogen, Cholinergic and Gabaergic Activity, and Memory

最近的研究表明雌激素可以影响认知过程。推测这些作用部分是由于雌激素通过影响基底前脑特定区域内的胆碱能和GABA能神经元来增强向海马和皮质的胆碱能投射的功能状态。拟议的对大鼠的研究将使用生物化学、药理学、和行为学技术研究雌激素替代对基底前脑胆碱能神经元和相应认知过程的影响。 一个主要的目标是验证雌激素替代可以减少与基底前脑胆碱能神经元丢失相关的认知障碍的假设。 这一目标将通过检测雌激素替代减少大鼠选择性胆碱能损伤引起的学习、记忆和注意力障碍的能力来实现。 另一个主要目的是检测雌激素降低GABA受体介导的胆碱能活性的能力。 这将通过体内微透析方法和检测雌激素阻止劳拉西泮引起的乙酰胆碱释放减少的能力来实现。这些研究将有助于提供一个综合的机制来解释雌激素替代如何影响基底前脑和海马中胆碱能和GABA能系统之间的相互作用，并将有助于确定雌激素替代治疗减少与胆碱能和GABA能活性改变相关的胆碱能损伤的潜在机制。

Recent studies suggest that estrogen can influence cognitive processes.It is hypothesized that these effects are due, in part, to the ability ofestrogen to enhance the functional status of cholinergic projections tothe hippocampus and cortex by affecting cholinergic and GABAergicneurons within specific regions of the basal forebrain.The proposed studieson rats will use a combination of biochemical,pharmacological, and behavioral techniques to examine the effects ofestrogen replacement on basal forebrain cholinergic neurons andcorresponding cognitive processes. One major goal is to test thehypothesis that estrogen replacement can reduce cognitive impairmentsassociated with the loss of basal forebrain cholinergic neurons. Thisgoal will be accomplished by examining the ability of estrogenreplacement to reduce impairments in learning, memory and attentionalprocesses produced by selective cholinergic lesions in rats. Anothermajor goal is to examine the ability of estrogen to reduceGABA-receptor-mediated effects on cholinergic activity. This will beaccomplished using an in vivo microdialysis approach and examining theability of estrogen to prevent decreases in acetylcholine releaseproduced by lorazepam.These studies will help provide an integrated, mechanistic account ofhow estrogen replacement influences interactions between cholinergic andGABAergic systems in the basal forebrain and hippocampus, and will helpto define potential mechanisms by which estrogen replacement can reducecognitive impairments associated with alterations in cholinergic andGABAergic activity.