Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: A detailed cellular in situ hybridization study

被引:117
作者
Augood, SJ
Faull, RLM
Love, DR
Emson, PC
机构
[1] UNIV AUCKLAND, DEPT ANAT, AUCKLAND, NEW ZEALAND
[2] UNIV AUCKLAND, SCH BIOL SCI, AUCKLAND, NEW ZEALAND
基金
英国惠康基金;
关键词
basal ganglia; striatal compartments; in situ hybridization; Huntington's disease; neuropeptide gene expression;
D O I
10.1016/0306-4522(95)00595-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [S-35]oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. The clinical and pathological diagnosis of Huntington's disease was confirmed unequivocally by genetic analysis of the CAG repeat length in both copies of IT15, the Huntington's disease gene. A marked reduction in both enkephalin and substance P messenger RNAs was detected in all regions of the caudate nucleus and putamen in Huntington's disease grades 2/3 when compared to controls; in the dorsal caudate few enkephalin or substance P messenger RNA-positive cells were detected. For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs was noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the ''indirect'' GABA/enkephalin and ''direct'' GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.
引用
收藏
页码:1023 / 1036
页数:14
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