DEPRESSION, 5 HT1A RECEPTOR, & NEUROPLASTICITY

描述(摘自申请者摘要)：5-羟色胺系统 已知在一些抑郁症患者中会减少。抑郁症，此外 由于它的情感成分，会产生学习和记忆缺陷， 通常与海马区的突触功能有关。这些认知 缺陷对增加5-羟色胺的药物治疗有反应。一次损失 5-羟色胺对大鼠突触素、MAP-2免疫反应的影响 以及皮质和海马区的非单胺能突触。而这些 神经元标志物减少，我们发现营养反应增加 以及5-HT-1a受体蛋白的抗肽标记。同样，在 抑郁的人，皮质中5-羟色胺的下降与 5-羟色胺-1A受体结合。在动物中，这种受体的激活通过一种 5-羟色胺-1A激动剂可迅速逆转5-羟色胺丢失所致的改变。这个 这项应用的长期目标是测试5-HT-1A的假设 受体调节成年海马神经元的波动性 成熟和不成熟的国家。具体地说，我们认为5-羟色胺的丢失将 诱导神经元树突回缩和5-羟色胺-1a的增加 受体蛋白和基因表达。我们预测5-羟色胺-1A受体 刺激能更有效地恢复成熟神经元的表型 三环类抗抑郁药或特定的5-羟色胺再摄取抑制剂。 5-羟色胺将被对氯苯丙氨酸(PCPA)还原， 对氯苯丙胺(PCA)或5，7-二羟色胺(5，7-DHT)和 用高效液相色谱法或帕罗西汀结合法测量。神经元的形态将是 研究并与使用5-HT-1A受体拮抗剂治疗的动物进行比较。 用我们的抗肽抗体标记的5-HT-1a受体将被研究 免疫细胞化学体内形态计量学和体外定量 缝隙印迹和免疫印迹。最后，我们将研究5-HT1a受体 用原位杂交法检测mRNA的表达。这些结果可能有助于理解 抑郁症和相关疾病的病因学，并为 有效和新颖的治疗方法。

DESCRIPTION (Adapted from applicant's abstract): The serotonin system is known to be decreased in some depressed patients. Depression, in addition to its affective component, produces deficits in learning and memory which are normally associated with hippocampal synaptic function. These cognitive deficits are responsive to treatment with drugs that increase 5-HT. A loss of 5-HT in rats produces a decrease in synaptophysin, MAP-2 immunoreactivity and non-monoaminergic synapses in cortex and hippocampus. While these neuronal markers are decreased, we found an increase of trophic responses and of antipeptide labeling of the 5-HT-1A receptor protein. Likewise, in depressed humans, a fall of 5-HT in cortex is associated with an increase in 5-HT-1A receptor binding. In animals, activation of this receptor with a 5-HT-1A agonist rapidly reverses the changes induced by 5-HT loss. The long-term aim of this application is to test the hypothesis that the 5-HT-1A receptor regulates the fluctuation of adult hippocampal neurons between mature and immature states. Specifically, we propose that loss of 5-HT will induce a retraction of neuronal dendrites and an increase in 5-HT-1A receptor protein and gene expression. We predict 5-HT-1A receptor stimulation will restore the mature neuronal phenotype more effectively than either tricyclic antidepressants or specific serotonin reuptake inhibitors. 5-HT will be reduced by para-chlorophenylalanine (PCPA), para-chloroamphetamine (PCA) or 5,7-dihydroxytryptamine (5,7-DHT) and measured by HPLC or paroxetine binding. The neuronal morphology will be studied and compared to animals treated with a 5-HT-1A receptor antagonist. 5-HT-1A receptors labeled with our antipeptide antibodies will be studied morphometrically in vivo by immunocytochemistry and quantified in vitro by slot blots and immunoblots. Finally we will examine the 5-HT1A receptor mRNA using in situ hybridization. These results may help understand the etiology of depression and related disorders and provide insights for effective and novel treatments.