GABA EFFECTS ON GNRH NEURONAL MIGRATION

促性腺激素释放激素神经元的正常功能 对于生物体的繁殖成功是必不可少的。在.期间 在发育过程中，GnRH神经元的迁移途径来自于它们的 嗅觉定位的外周出生地，在筛状突对面 最后到达它们在基底前脑(BF)的目的地。这些 神经元沿着嗅觉纤维迁移。这些纤维的断裂 在发育过程中会导致嗅觉障碍。性腺功能减退。其作用机制 导致这种相对独特的迁徙的因素在很大程度上是未知的。 初步数据显示，神经递质γ-氨基丁酸 酸(GABA)可能在调节GnRH神经元迁移中发挥作用。我们 已经开发出一种切片制剂，它保持了 GnRH迁移途径。目前的提案重点是3个具体的 这种GABA效应的各个方面。第一，三者的参与 将通过定位特定的GABA受体来研究 用免疫细胞化学的方法研究这些沿迁移路线的受体 并在体外通过激活胚胎切片中的特异性受体。 第二，钙离子在GABA介导的GnRH神经元迁移中的作用将 通过使用钙通道阻滞剂和钙离子进行研究 螯合剂除GABA能药物外，还有体外试验。第三，在场 GnRH神经元亚群中GABA的分布将在两个 方式。首先，在这些GnRH神经元中发现GABA的过程 将通过免疫细胞化学来探索合成酶 谷氨酸脱羧酶(GAD 65和GAD 67)或醛 脱氢酶(AD)和GABA转运蛋白GAT-1。二、角色定位 GnRH神经元中GABA在GABA介导的GnRH神经元迁移中的作用 通过使用GAD和AD抑制剂以及GAT阻滞剂进行研究 除了GABA能药物外，还有体外试验。

The proper functioning of gonadotropin releasing hormone (GnRH) neurons is necessary for the reproductive success of an organism. During development, the migratory route of GnRH neurons proceeds from their peripheral birthplace in the olfactory placode, across the cribriform plate and to their final destination in the basal forebrain (BF). These neurons migrate along olfactory fibers. The disruption of these fibers during development results in anosmia. and hypogonadism. The mechanisms that contribute to this relatively unique migration are largely unknown. Preliminary data suggest that the neurotransmitter gamma-aminobutyric acid (GABA) may play a role in regulating GnRH neuronal migration. We have developed a slice preparation which maintains the integrity of the GnRH migratory pathway. The current proposal focuses on 3 specific aspects of this GABA effect. First, the involvement of the three specific GABA receptors will be investigated through localization of these receptors along the migratory route by use of immunocytochemistry and through specific receptor activation in embryonic slices in vitro. Second, the role of Ca2+ in GABA-mediated GnRH neuronal migration will be investigated through the use of Ca2+ channel blockers and Ca2+ chelators in addition to GABAergic drugs in vitro. Third, the presence of GABA in a subpopulation of GnRH neurons will be investigated in two ways. First, the process by which GABA is found in these GnRH neurons will be explored by immunocytochemistry for the synthesizing enzymes glutamic acid decarboxylase (GAD 65 and GAD 67) or aldehyde dehydrogenase (AD) and the GABA transporter, GAT-1. Second, the role of GABA in GnRH neurons in GABA-mediated GnRH neuronal migration will be studied through the use of GAD and AD inhibitors, and GAT blockers in addition to GABAergic drugs in vitro.