DEPRESSION, 5-HT1A RECEPTOR & NEUROPLASTICITY

描述：（改编自申请人的摘要）抑郁症与 情感和认知障碍。申请人认为其中一些症状 可能是由于海马和皮质形态（细胞骨架）的丧失 由于5-羟色胺的丢失而引起的虚脱。成年大鼠血清素丢失 大脑产生减少的树突长度，树突棘数量和大小， 突触数量和免疫反应性的减少， 神经元（微管相关蛋白-2和突触素）和神经胶质 （S-100 n）标记。注射5-HT 1A拮抗剂产生类似的损失， 突触和树突棘。神经元和神经胶质标记物的丢失是 通过用5-HT 1A受体激动剂和S-100 β治疗逆转。此续订 应用程序将测试假设，5-HT 1A受体稳定 神经细胞骨架靶向神经元和神经胶质细胞，并可能保护 凋亡（apoptosis）。 申请人希望继续并扩大我们对以下影响的研究： 5-HT药物对5-HT丢失后形态学逆转的作用 格兰特.此外，申请人现在提出5-HT 1A受体可以调节 神经元的细胞骨架，通过作用于神经胶质细胞（S100 f3的可用性） 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-HT 1A是否 受体刺激或S100 β治疗将恢复细胞骨架 在接触了coichicine之后。Coichicine促进微管分解， 在培养和体内促进细胞凋亡。 大鼠将注射对氯苯丙胺（PCA），以降低5-HT水平 申请人将用5-HT 1A受体拮抗剂， 三环类、5-羟色胺特异性再摄取抑制剂（SSRJ）或MAO-A抑制剂。 此外，申请人将研究可能的作用机制， 将培养的神经元暴露于5-HT 1A受体激动剂和S-100 β。的 申请人希望将这项工作扩展到初级海马和皮层 使用野生型和敲除（S100 β和 5-HT 1A受体）小鼠。最后，研究了S-HT 1A激动剂和S-100 β的作用。 将秋水仙碱微量注射到成年大鼠后进行研究 海马体和皮层。申请人将专注于树突状崩溃， 神经元凋亡。这项工作将继续我们的长期研究， 5-羟色胺和成人可塑性之间的相互作用。

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.