Effects of Specific MAO Inhibitors on Cultured 5-HT Neurons

5-羟色胺在神经发育中起着重要作用， 改变前脑的性质，神经突起的生长， 突触后受体，并对抑制性 行为。 这项研究将集中在一个命题， 5-HT对肾上腺素能神经元作用的成分 （自身调节）可能是其细胞内代谢的单胺 氧化酶（MAO）。 这个假设是基于这样一个事实， 通过MAO代谢5-HT产生H2O2，其具有高毒性 因为它能形成羟基自由基。 酶 MAO有两种形式，A和B。 MAO-A具有更高的亲和力， 对于5-HT比MAO-B，但后者的形式是本地化， 神经元和星形胶质细胞。 初步研究表明，MAO-B的抑制是 有效促进胎儿5-HT发育。 这些研究 由于单胺的广泛使用， 氧化酶抑制剂在抑郁症患者中的作用 还有助于 了解老年痴呆症背后与年龄相关的退行性过程 由于MAO-B在衰老过程中增加， 在学习和记忆中起重要作用的神经元数量减少。

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.