Effects of Specific MAO Inhibitors on Cultured 5-HT Neurons

特定 MAO 抑制剂对培养 5-HT 神经元的影响

• 批准号: 8812892
• 负责人: Efrain Azmitia
• 金额: $ 22.26万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-10-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8812892&HistoricalAwards=false
• 关键词: Effects; Specific; MAO; Inhibitors; Cultured

Serotonin plays an important role in neurodevelopment by causing changes in forebrain naturation, neurite outgrowth, expression of postsynaptic receptors, and on the apprearance of inhibitory behaviors. This research will focus on the proposition that a component of the action of 5-HT on serotonergic neurons (autoregulation) may be its intracellular metabolism by monoamine oxidase (MAO). The hypothesis is based on the fact that metabolism of 5-HT by MAO generates H202, which is highly toxic to neurons because it can form hydroxy-free radicals. The enzyme MAO exists in two forms, A and B. MAO-A has a higher affinity for 5-HT than MAO-B, but this latter form is localized to serotonergic neurons and astrocytes. Preliminary studies indicate that inhibition of MAO-B is effective in augmenting fetal 5-HT development. The studies are clinically relevant because of the widespread use of monoamine oxidase inhibitors in depressed patients. They may also help understand age-related degenerative processes underlying dementia since MAO-B is increased during aging while serotonergic neurons, important in learning and memory, are reduced.

5 -羟色胺通过改变前脑自然、神经突生长、突触后受体的表达以及抑制行为的出现，在神经发育中发挥重要作用。本研究将重点探讨5-羟色胺对血清素能神经元（自调节）作用的一个组成部分可能是其通过单胺氧化酶（MAO）在细胞内的代谢。这一假设是基于MAO代谢5-HT产生H202这一事实，H202对神经元具有高度毒性，因为它可以形成羟基自由基。MAO酶以A和b两种形式存在。MAO-A比MAO- b对5-羟色胺有更高的亲和力，但后者局限于血清素能神经元和星形胶质细胞。初步研究表明，抑制MAO-B可有效促进胎儿5-羟色胺的发育。由于单胺氧化酶抑制剂在抑郁症患者中的广泛应用，这些研究具有临床相关性。它们也可能有助于理解痴呆背后与年龄相关的退行性过程，因为MAO-B在衰老过程中增加，而对学习和记忆很重要的血清素能神经元则减少。