DEPRESSION, 5-HT1A RECEPTOR & NEUROPLASTICITY

描述：(摘自申请者的摘要)抑郁症与 情感和认知障碍。申请者提出了其中一些症状 可能是由于海马区和皮质形态的丧失(细胞骨架 崩溃)由于5-羟色胺的丧失而引起的。成年大鼠5-羟色胺的丢失 大脑产生树突长度、树突棘数量和大小减少， 突触数量与抗肿瘤抗体免疫反应性降低 神经元(微管相关蛋白-2和突触素)和胶质细胞 (S-龙)记分员。注射5-HT1a拮抗剂也会产生类似的损失 突触和树突。神经元和神经胶质标志物的丢失是 经5-HTIA受体激动剂和S-100β治疗后逆转。此次续订 应用程序将检验5-HT1a受体稳定 通过靶向神经元和神经胶质细胞的神经元细胞骨架，并可能保护 神经元死亡(细胞凋亡)。 申请者希望继续并扩大我们对 5-羟色胺药物对5-羟色胺丢失后形态逆转的初步研究 格兰特。此外，申请者现在提出5-HT1a受体可能调节 神经元的细胞骨架，通过两者作用于胶质细胞(S100f3上市) 和神经元(受体诱导的磷酸化途径的变化(例如，PKC， PKA和MAPK))。此外，申请人希望测试5-HT1A是否 受体刺激或S 10β治疗可恢复细胞骨架 在接触了可可西汀之后。Coichicine促进微管解体和 促进培养和体内的细胞凋亡。 大鼠将被注射对氯苯丙胺(PCA)以降低5-羟色胺水平 申请人将用5-HT1a受体拮抗剂治疗这些大鼠， 三环类药物，5-羟色胺特异性再摄取抑制剂(SSRJ)或MAO-A抑制剂。 此外，申请者还将研究下列可能的行动机制 5-HT1a受体激动剂和S-100β对培养神经元的作用。这个 申请者希望将这项工作扩展到初级海马和大脑皮层 使用野生型和基因敲除(S100 beta和 5-HT1A受体)小鼠。S-HT1a激动剂和S-100β的作用 将在成年大鼠体内微量注射秋水仙碱后进行研究 海马体和皮质。申请者将专注于树枝状坍塌和 神经细胞的凋亡。这项工作将继续我们对 5-羟色胺与成人肺可塑性的相互作用。

DESCRIPTION: (Adapted from applicant's abstract) Depression is associated with affective and cognitive disorders. The applicant suggest some of these symptoms may be due to loss of hippocampal and cortical morphology (cytoskeletal collapse) induced by loss of serotonin. Loss of serotonin in the adult rat brain produces decreased dendritic length, dendritic spine number and size, synapse number and a reduction in immunoreactivity to antibodies against neuronal (Microtubule Associated Protein-2 and synaptophysin) and glial (S-lOOn) markers. Injection with a 5-HT1A antagonist produces similar loss of synapses and dendritic spines. The loss of neuronal and glial markers is reversed by treatment with 5-HTIA receptor agonists and S-100beta. This renewal application will test the hypothesis that the 5-HT1A receptor stabilize the neuronal cytoskeletal by targeting neurons and glial cells, and may protect neurons from death (apoptosis). The applicant would like to continue and expand our studies on the effects of 5-HT drugs on morphological reversal after 5-HT loss proposed in the onginal grant. In addition, the applicants now propose the 5-HT1A receptor may regulate the cytoskeleton of neurons, by acting both on glial (availability of S100f3) and neurons (receptor-induced changes in phosphorylation pathways (e.g. PKC, PKA and MAPK)). In addition, The applicant would like to test if 5-HT1A receptor stimulation or S lOObeta treatmnent will restore the cytoskeleton after exposure to coichicine. Coichicine promotes microtubule disassembly and promotes apoptosis in culture and in vivo. Rats will be injected with para-chloroamphetamine (PCA) to reduce 5-HT levels The applicant will treat these rats with either a 5-HT1A receptor antagonist, tricyclics, serotonin specific reuptake inhibitors (SSRJ) or MAO-A inhibitor. In addition, the applicants will study possible mechanisms of action after exposure of cultured neurons to 5-HT1A receptor agonist and S-lOObeta. The applicants hope to extend this work to primary hippocampal and cortical neuronal and glial cultures using wild type and knockout (S100beta and the 5-HT1A receptor) mice. Finally, the actions of S-HT1A agonist and S-lOObeta will be studied after microinjections of colchicine into the adult rat hippocampus and cortex. The applicant will focus on dendritic collapse and apoptosis of neurons. This work will continue our long-term research into the interactions between serotonin and adult neumplasticity.