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

5-羟色胺（5-HT）与大脑的可塑性有关，在新生儿期遭受6-羟多巴胺（6-OHDA）损伤的大鼠的新纹状体中会出现5-HT异型发芽。6-OHDA分别于动物（大鼠和小鼠）出生后3天、7天、12天和28天给予右侧脑室。6-OHDA给药后第2天、第5周、第10周和第1年经心灌注。用抗酪氨酸羟化酶（TH）和抗5- ht抗体进行免疫组化研究。同时进行nadph - diaphase组织化学。采用NIH图像在三个冠状水平对nadph阳性细胞和纤维末梢进行定量分析。这项研究表明，即使在出生后12天，患有同种单侧6-羟色胺损伤的小鼠纹状体中也出现了显著的5 -羟色胺纤维的过度神经支配。这是多巴胺去神经后血清素能异型萌发关键期的重要发现。值得注意的是，内在的5 -羟色胺能异型发芽在整个研究过程中持续存在，即在6-羟色胺损伤后一年，这表明发芽是持久的。多巴胺耗竭后，纹状体中5 -羟色胺能异型萌发过程中nadph阳性结构密度无显著变化。这是首次证明5-HT高神经支配发生在6-OHDA损伤小鼠的新纹状体，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.