Molina-Holgado E, Dewar K M, Grondin L, van Gelder N M, Reader T A
Département de Physiologie, Faculté de Médecine, Université de Montréal, Quebec, Canada.
J Neurosci Res. 1993 Jul 1;35(4):409-18. doi: 10.1002/jnr.490350408.
The effects of a neonatal dopaminergic deafferentation with the neurotoxin 6-hydroxydopamine (6-OHDA) on endogenous tissue levels of catecholamines, indoleamines, and amino acids were investigated in discrete rat brain regions. After producing the lesion at postnatal day 3 by intraventricular injections of 6-OHDA, with a desipramine pretreatment to protect noradrenaline neurons, the animals were kept for 3 months. Their brains were dissected to obtain samples of neostriatum, Globus pallidus, Substantia nigra, and Raphe nuclei, which were then analyzed by high-performance liquid chromatography, coupled either to electrochemical detection for aromatic monoamines, or to post-column ninhydrin derivatization with spectrophotometry for amino acids. The neonatal 6-OHDA treatment depleted dopamine (DA) levels in neostriatum, Globus pallidus, and Substantia nigra, but in Raphe nuclei DA was increased. The main metabolites of DA were also decreased in neostriatum, Globus pallidus, and Substantia nigra but remained unchanged in Raphe nuclei. Serotonin (5-HT) and its metabolite 5-hydroxy-indole-3-acetic acid increased in neostriatum and Raphe nuclei; in Substantia nigra there was a slight increase in 5-HT only. The 6-OHDA lesion caused heterogeneous alterations in amino acid contents, which varied according to the region. In the neostriatum there were increases of gamma-aminobutyric acid (GABA), aspartic acid, and glycine. In the Globus pallidus taurine, GABA, glutamic acid, glutamine, aspartic acid, serine, and alanine were elevated. In the Substantia nigra only increases in taurine, GABA, glutamic acid, and glutamine could be documented. This study shows important changes in amino acid levels and in some of their ratios, occurring in different anatomical subdivisions of the basal ganglia and related brainstem nuclei following a neonatal treatment with 6-OHDA. The results thus demonstrate major biochemical modifications in amino acids in the aftermath of a DA denervation and/or a 5-HT hyperinnervation during an early developmental period.
研究了用神经毒素6-羟基多巴胺（6-OHDA）进行新生鼠多巴胺能去传入对大鼠离散脑区儿茶酚胺、吲哚胺和氨基酸内源性组织水平的影响。在出生后第3天通过脑室内注射6-OHDA造成损伤，并预先用去甲丙咪嗪保护去甲肾上腺素能神经元，将动物饲养3个月。解剖它们的大脑以获取新纹状体、苍白球、黑质和中缝核的样本，然后通过高效液相色谱进行分析，该色谱与用于芳香单胺的电化学检测或与用于氨基酸的柱后茚三酮衍生化分光光度法联用。新生鼠6-OHDA处理使新纹状体、苍白球和黑质中的多巴胺（DA）水平降低，但中缝核中的DA增加。新纹状体、苍白球和黑质中DA的主要代谢产物也减少，但中缝核中的代谢产物保持不变。血清素（5-HT）及其代谢产物5-羟基吲哚-3-乙酸在新纹状体和中缝核中增加；黑质中仅5-HT略有增加。6-OHDA损伤导致氨基酸含量发生异质性改变，其因区域而异。新纹状体中γ-氨基丁酸（GABA）、天冬氨酸和甘氨酸增加。苍白球中的牛磺酸、GABA、谷氨酸、谷氨酰胺、天冬氨酸、丝氨酸和丙氨酸升高。黑质中仅记录到牛磺酸、GABA、谷氨酸和谷氨酰胺增加。本研究表明，新生鼠用6-OHDA处理后，基底神经节和相关脑干核的不同解剖亚区的氨基酸水平及其某些比例发生了重要变化。因此，结果证明了在早期发育阶段多巴胺去神经支配和/或5-羟色胺超神经支配后氨基酸的主要生化改变。
