Studies on the role of the serotonergic neuron system in the plasticity of the developing brain

5-羟色胺（5-HT）与脑的可塑性有关，在新生期6-羟基多巴胺（6-OHDA）损伤的大鼠新纹状体中出现5-HT异型发芽。6-在出生后3天、7天、12天和28天，将OHDA施用到动物（大鼠和小鼠）的右侧脑室。于6-OHDA给药后2天、5周、10周和1年分别行心脏灌流，用抗酪氨酸羟化酶（TH）和抗5-羟色胺（5-HT）抗体进行免疫组化研究。还进行了NADPH黄递酶组织化学。用NIH Image对3个冠状面的NADPH阳性细胞和纤维终末进行定量分析，结果表明，在出生后12天，同样单侧6-OHDA损伤的小鼠纹状体内5-羟色胺纤维出现明显的高神经支配。这是一个重要的发现，多巴胺去神经后的多巴胺能异型发芽的关键时期。值得注意的是，在整个研究过程中，即6-OHDA损伤后一年，内源性β-肾上腺素能异型发芽持续存在，表明发芽持续时间长。多巴胺耗竭后，纹状体中NADPH阳性结构的密度在多巴胺能异型发芽的发展过程中没有显着变化。这是第一次证明，5-HT超神经支配发生在新纹状体的小鼠遭受6-OHDA损伤，甚至在出生后12天，5-HT异型发芽可能是永久性的。

Serotonin (5-HT) is related to the plasticity of the brain, and 5-HT heterotypic sprouting occurs in the neostriatum of rats that suffer 6-hydroxydopamine (6-OHDA) lesioning in the neonatal period. 6-OHDA was administered to the right lateral ventricle of animals (rat and mouse) at 3 days, 7 days, 12 days and 28 days after birth. Then the animals were perfused transcardially at 2 days, 5 weeks, 10 weeks and 1 year after the administration of 6-OHDA.Immunohistochemical studies were performed with anti-tyrosine hydroxylase (TH) and anti-5-HT antibodies. NADPH-diaphorase histochemistry was also performed. Quantitative analysis on NADPH-positive cells and fiber terminals were performed using NIH Image at three coronal levels.This study has shown that remarkable hyperinnervation of serotonin fibers occurred in the striatum of mice that had undergene the same kind of unilateral 6-OHDA lesioning at even 12 days after birth. This is an important finding as to the critical period for serotonergic heterotypic sprouting after dopamine denervation. Noteworthy is that intrinsic serotonergic heterotypic sprouting persisted throughout the time course of the study, namely, to one year after 6-OHDA lesioning, suggesting that the sprouting is long lasting. There is no significant change in the density of NADPH-positive structures in the striatum during the development of serotonergic heterotypic sprouting after dopamine-depletion. This is the first demonstration that 5-HT hyperinnervation occurs in the neostriatum of mice suffering 6-OHDA lesioning at even 12 days after birth, and that 5-HT heterotypic sprouting may be permanent.