DEPRESSION, 5 HT1A RECEPTOR, & NEUROPLASTICITY

描述（改编自申请人的摘要）：血清素系统是 在一些抑郁症患者中会减少 抑郁症，此外 它的情感成分，产生缺陷的学习和记忆， 通常与海马突触功能有关。 这些认知 缺乏对增加5-HT的药物治疗有反应。 亏损 5-HT可使突触素、MAP-2免疫反应性降低， 以及皮层和海马中的非单胺能突触。 虽然这些 神经元标记物减少，我们发现营养反应增加 和5-HT-1A受体蛋白的抗肽标记。 同样，在 抑郁的人，皮质中5-HT的下降与 5-HT-1A受体结合。 在动物中，这种受体的激活与 5-HT-1A激动剂可迅速逆转5-HT丢失引起的变化。 的 本申请的长期目的是检验5-HT-1A 受体调节成年海马神经元之间的波动 成熟和不成熟的国家。 具体来说，我们认为5-HT的丢失将 诱导神经元树突收缩和5-HT-1A增加 受体蛋白和基因表达。 5-HT-1A受体 刺激将更有效地恢复成熟的神经元表型， 三环类抗抑郁药或特异性血清素再摄取抑制剂。 5-HT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）， 通过HPLC或帕罗西汀结合测量。 神经元形态学将是 研究并与用5-HT-1A受体拮抗剂处理的动物进行比较。 我们的抗肽抗体标记的5-HT-1A受体将被研究 通过免疫细胞化学在体内进行形态测定，并通过 狭缝印迹和免疫印迹。 最后，我们将研究5-HT 1A受体 mRNA的原位杂交。 这些结果可能有助于理解 抑郁症和相关疾病的病因学，并提供见解， 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.