MELATONIN EFFECTS ON DAMAGED DOPAMINE NEURONS

描述多巴胺(DA)神经元特别容易受到损伤和细胞 死亡，而它们在人类中的丢失与疾病有关，包括 帕金森氏病(PD)。有大量证据表明 帕金森病患者多巴胺能神经元的破坏与游离的蓄积有关 激进分子。抗氧化荷尔蒙，褪黑素，是最有效的 内源性氧自由基清除剂，但其拯救、预防或 DA神经元的修复损伤尚未被直接研究。这项建议 寻求在几个实验室模型中测试褪黑素对DA神经元的影响 与氧化应激有关，包括生长因子缺乏或 MPP+或6-OHDA的神经毒性损伤。初步研究显示， 褪黑素抢救发育中和神经毒素损伤的显著能力 DA神经元在培养和体内即将到来的细胞死亡中的作用 促进DA纤维的生长和再生。这样做的最终目的是 研究是为了更全面地了解褪黑素 可能在增加受损的DA系统中神经元的存活率方面发挥作用 为开发帕金森病等疾病的治疗方法奠定了基础 使用受损的DA系统。

DESCRIPTION Dopamine (DA) neurons are uniquely vulnerable to damage and cell death, and their loss in humans is associated with diseases including Parkinson's disease (PD). There is a large body of evidence suggesting that the destruction of DA neurons in PD involves the accumulation of free radicals. The antioxidant hormone, melatonin, is one of the most potent endogenous scavengers of oxyradicals yet its ability to rescue, prevent or repair damage to DA neurons has not been directly studied. This proposal seeks to test melatonin's effects on DA neurons in several laboratory models associated with oxidative stress, including growth factor deprivation or neurotoxic injury from MPP+ or 6-OHDA. Preliminary studies reveal a remarkable ability of melatonin to rescue developing and neurotoxin- damaged DA neurons from impending cell death in culture and in vivo and to further promote the growth and regeneration of DA fibers. The ultimate goal of this research is to provide a fuller understanding of the role that melatonin might play in increasing the survival of neurons in the injured DA system and lay a foundation for development of treatments for PD and other diseases with compromised DA systems.