Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France.
Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France; Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy.
Neurochem Int. 2019 Sep;128:186-195. doi: 10.1016/j.neuint.2019.05.001. Epub 2019 May 2.
Huntington's disease (HD) is a rare, autosomal neurodegenerative disease characterized by motor and cognitive impairments appearing in adults. The R6/1 mouse model of the disease recapitulates the adult onset of motor symptoms preceded by cognitive and affective deficits. The monoaminergic systems participate in the establishment of motor and cognitive loops and we postulated that their organization and interaction could be precociously altered. Using tissue measurement of dopamine (DA), serotonin (5-HT), noradrenaline, and some metabolites, we observed that DA and/or its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-HT or noradrenaline tissue content was reduced in an age-dependent manner (from two to six months) in the striatum, substantia nigra and globus pallidus of R6/1 mice. The metabolite of 5-HT was also lower in R6/1 mice, mainly in the substantia nigra and hippocampus. We then addressed early disorganization of monoaminergic systems in 18 brain regions encompassing several neurobiological networks in 35 day-old animals. DA tissue content was not altered in the striatum or substantia nigra but was decreased in the nucleus accumbens and increased in the globus pallidus. The correlations of monoaminergic index in-between the 18 selected brain regions revealed distinct organizations of monoamines in R6/1 mice, notably marked by a loss of the number of correlations of the DOPAC/DA ratio. The neurochemical analyses show that each monoaminergic system is distinctly altered in the R6/1 mouse model. The early abnormal organization of these systems likely points out altered maturation of neurobiological networks at early stages of HD.
亨廷顿病（HD）是一种罕见的常染色体神经退行性疾病，其特征是成年期出现运动和认知障碍。该疾病的 R6/1 小鼠模型再现了运动症状的成人发病，伴有认知和情感缺陷。单胺能系统参与运动和认知回路的建立，我们推测它们的组织和相互作用可能会过早改变。使用多巴胺（DA）、5-羟色胺（5-HT）、去甲肾上腺素和一些代谢物的组织测量，我们观察到 DA 和/或其代谢物 3,4-二羟基苯乙酸（DOPAC），而不是 5-HT 或去甲肾上腺素的组织含量在 R6/1 小鼠中以年龄依赖的方式（从两个月到六个月）降低。5-HT 的代谢物在 R6/1 小鼠中也较低，主要在黑质和海马体中。然后，我们在 35 天大的动物的 18 个脑区中解决了单胺能系统的早期失调问题，这些脑区涵盖了几个神经生物学网络。纹状体或黑质中的 DA 组织含量没有改变，但伏隔核中的 DA 组织含量降低，苍白球中的 DA 组织含量增加。在 18 个选定脑区之间的单胺能指数相关性分析表明，R6/1 小鼠中的单胺能系统存在不同的组织，特别是 DOPAC/DA 比值的相关性数量减少。神经化学分析表明，R6/1 小鼠模型中的每个单胺能系统都发生了明显改变。这些系统的早期异常组织可能表明在 HD 的早期阶段神经生物学网络的成熟发生改变。
