TRH AND NEURONAL APOPTOSIS

促甲状腺激素释放激素（TRH）在下丘脑外的作用 中枢神经系统（CNS）的区域尚不清楚，但已 被认为是一种神经递质或神经调节剂， 地点 已经认识到各种神经肽， 包括P物质（SP）在内的多种神经营养因子可能起着神经营养因子的作用。 最近，我们的实验室报告（在摘要中）， 胎鼠下丘脑培养物与腺病毒含有 反义大鼠TRH cDNA导致神经元细胞死亡。 这一发现 提出了TRH可能不仅作为一种 下丘脑释放因子，也作为神经营养因子， CNS。 许多神经营养因子（或保护神经元的因子） 完整性）已在CNS中描述，包括脑源性 神经营养因子（BDNF），已被报道是共定位的 与TRH 因此我们推测TRH和BDNF可能存在协同作用 作为CNS中的神经营养因子（或作为细胞凋亡抑制剂）。 也有证据表明BDNF与bcl-2家族相互作用， 原癌基因在调节凋亡过程中的作用。 一个可能 TRH“敲除”可诱导神经元死亡的机制 TRH可能与BDNF协同作用影响细胞凋亡， 作为凋亡过程的抑制剂或作为bcl-2 激活剂，刺激bcl-2，防止细胞死亡。 这项提议旨在检验TRH是一种 神经营养因子是维持神经元所必需的。 CNS，并通过Bcl-2家族与BDNF合作。 原癌基因在神经元凋亡过程中的作用。 这些研究 可能与退行性神经系统疾病的发病机制有关 阿尔茨海默病或帕金森病等疾病 正常的收获。

The role of Thyrotropin Releasing Hormone (TRH) in extra hypothalamic areas of the central nervous system(CNS) is unclear but has been thought to act as a neurotransmitter or neuromodulater in these locations. It has been recognized that various neural peptides, including substance P (SP), may function as neurotropic factors. Recently, our laboratory reported (in abstract) that transfection of fetal rat hypothalamic cultures with an adenovirus containing an antisense rat TRH cDNA led to neuronal cell death. This finding raises the possibility that TRH may function not only as an hypothalamic releasing factor but also as a neurotrophic factor in CNS. A number of neurotrophins (or factors that preserve neuronal integrity) have been described in the CNS including brain-derived neurotrophic factor (BDNF) which has been reported to be colocalized with TRH. Accordingly we speculate that TRH and BDNF may cooperate as neurotrophic factors (or as inhibitor of apoptosis) in the CNS. There is also evidence that BDNF interacts with the bcl-2 family of protooncogenes in regulating the apoptotic process. A possible mechanism through which a TRH "knockout" could induce neuronal death is that TRH may cooperate with BDNF to influence the apoptosis, either as an inhibitor of the apoptosis process or as a bcl-2 activator to stimulate bcl-2 to prevent cell death. This proposal is designed to test the hypothesis that TRH is a neurotrophic factor necessary for the maintenance of neurons in the CNS and that it cooperates with BDNF through the Bcl-2 family of protooncogenes in the process of neuronal apoptosis. These studies may have relevance to the pathogenesis of degenerative neurologic disorders such as Alzheimer's disease or Parkinson's disease as well as normal gaining.