ESTROGEN AND NEUROTRANSMITTER SYSTEMS IN HIPPOCAMPUS

与学习和记忆相关的神经元可塑性 癫痫样活动依赖于两者活动的精确平衡。 海马区的主要神经递质系统：兴奋性 谷氨酸/天冬氨酸神经元与抑制性γ-氨基丁酸 (GABA)神经元。这项研究的目的是检验这一假说 雌二醇和黄体酮影响认知过程和 谷氨酸和/或氨基丁酸与癫痫发作的相互作用 神经元或其感受器系统。雌二醇会增加血管密度 NMDA、GABAA和孕激素受体以及树突棘和突触 在海马区的CA1区形成。雌二醇可能起作用1) 通过改变构象和结合性质直接作用于受体 2)通过增加转录和合成在基因上 或3)神经递质释放，进而 影响受体结合。为了评估雌二醇的影响 在谷氨酸和/或GABAA受体系统上，基因水平 NMDA和GABAA受体基因的表达将使用 原位杂交组织化学。行动的地点和重要性 将通过植入抗雌激素来评估突触传递 进入内嗅皮层，它有一个主要的投射到 或进入雌二醇组大鼠的背侧海马区，以及 测定NMDA和GABAA受体结合部位和mRNA水平。这个 抗雌激素植入物将阻断雌二醇的局部效应。在……里面 此外，雌二醇对神经递质合成和分泌的影响 将对释放进行评估。信使核糖核酸水平和酶活性 谷氨酸脱羧酶(GAD)是合成GABA的酶，将 作为GABA神经元活动大小的一个指标进行测量。 孕激素受体与GAD的免疫细胞化学共定位 将进行肽检测，以确定该机制是否存在 孕酮对GAD基因表达的直接作用。差异化 黄体酮作用于细胞内孕酮的作用 受体通过其代谢物别孕酮的作用而产生 在GABAA受体，动物将接受别孕酮治疗。 如果别孕酮模拟孕酮对GAD基因的作用 表达，则孕酮作用于GABAA受体。这个 这些研究的结果将有助于我们了解 雌激素对某些细胞因子影响的细胞机制 学习记忆和癫痫样活动的行为方面。

The neuronal plasticity associated with learning and memory and epileptiform activity depends on precise balances in the activity of two major neurotransmitter systems in the hippocampus: the excitatory glutamate/aspartate neurons and the inhibitory gamma-aminobutyric acid (GABA) neurons. The objective of this research is to test the hypothesis that estradiol and progesterone influence cognitive processes and epileptic seizure activity by interacting with the glutamate and/or GABA neurons or their receptor systems. Estradiol increases the density of NMDA, GABAA, and progesterone receptors and dendritic spines and synapse formation in the CA1 region of the hippocampus. Estradiol may act 1) directly at the receptor by changing conformation and binding properties of the protein, 2) at the gene by increasing transcription and synthesis of receptor subunits, or 3) on neurotransmitter release which in turn affects receptor binding. In order to assess the influence of estradiol on the glutamate and/or GABAA receptor systems, the levels of gene expression of NMDA and GABAA receptor genes will be determined using in situ hybridization histochemistry. The site of action and importance of synaptic transmission will be assessed by implantation of an antiestrogen into the entorhinal cortex, which has a major projection to the hippocampus or into the dorsal hippocampus of estradiol-treated rats and measuring NMDA and GABAA receptor binding sites and mRNA levels. The antiestrogen implants will block the local effects of estradiol. In addition, the effects of estradiol on neurotransmitter synthesis and release will be assessed. The levels of mRNA and the enzymatic activity of glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, will be measured as an indicator of the magnitude of GABA neuronal activity. Immunocytochemical colocalization of progesterone receptor and GAD peptide will be done to determine whether the mechanism exists for the direct action of progesterone on GAD gene expression. To differentiate the action of progesterone which acts at the intracellular progesterone receptor from the actions of its metabolite, allopregnanolone, which acts at the GABAA receptor, animals will be treated with allopregnanolone. If allopregnanolone mimics the action of progesterone on GAD gene expression, then progesterone is acting at the GABAA receptor. The results of these studies will contribute to our understanding of the cellular mechanisms underlying the effects of estradiol on certain behavioral aspects of learning and memory and epileptiform activity.