Striosomes and mood dysfunction in Huntington's disease.
Striosomes and mood dysfunction in Huntington's disease.
复制标题
DOI：
10.1093/brain/awl243
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
L. Tippett;H. Waldvogel;Sally Thomas;V. Hogg;W. V. van Roon-Mom;B. Synek;A. Graybiel;R. Faull
中科院分区：
文献类型：
--
作者：
L. Tippett;H. Waldvogel;Sally Thomas;V. Hogg;W. V. van Roon-Mom;B. Synek;A. Graybiel;R. Faull
可变表型在具有单基因遗传模式的神经系统疾病中很常见。在亨廷顿病中，情绪和认知症状与运动症状不同程度地共同表达。纹状体的两个主要神经化学区室（纹状体和纹状体外基质）中的神经元也存在不同程度的变性。为了确定亨廷顿病的表型变异是否与这种区室组织有关，我们进行了一项双盲研究，其中使用GABA（A）受体免疫组织化学分析了35例亨廷顿病病例和13例对照病例大脑中纹状体和基质的状态，并从家庭成员和记录中收集了患者表达的临床症状的详细数据。我们在此报告亨廷顿病患者明显的情绪功能障碍与纹状体纹状体内 GABA(A) 受体标记的差异性丢失之间存在显着关联。这种关联适用于症状的临床发作和末期评估。纹状体异常严重的病例进一步表现出发病年龄较晚、疾病级别较低以及HD基因中CAG重复长度较低。然而，我们发现 CAG 重复长度或发病年龄与情绪功能障碍之间没有独立关联。我们认为亨廷顿病临床症状的变化与纹状体纹状体和基质区室中 GABA(A) 受体表达的相对异常变化有关，并且纹状体相关回路可能调节情绪功能。
Variable phenotype is common in neurological disorders with single-gene inheritance patterns. In Huntington's disease, mood and cognitive symptoms are variably co-expressed with motor symptoms. There is also variable degeneration of neurons in the two major neurochemical compartments of the striatum, the striosomes and the extrastriosomal matrix. To determine whether the phenotypic variability in Huntington's disease is related to this compartmental organization, we carried out a double-blind study in which we used GABA(A) receptor immunohistochemistry to analyse the status of striosomes and matrix in the brains of 35 Huntington's disease cases and 13 control cases, and collected detailed data on the clinical symptomatology expressed by the patients from family members and records. We report here a significant association between pronounced mood dysfunction in Huntington's disease patients and differential loss of the GABA(A) receptor marker in striosomes of the striatum. This association held for both clinical onset and end-stage assessments of symptoms. The cases with accentuated striosome abnormality further exhibited later onset age, lower disease grade and lower CAG repeat length in the HD gene. We found no independent association, however, between CAG repeat length or age of onset and mood dysfunction. We suggest that variation in clinical symptomatology in Huntington's disease is associated with variation in the relative abnormality of GABA(A) receptor expression in the striosome and matrix compartments of the striatum, and that striosome-related circuits may modulate mood functioning.