Richfield E K, Maguire-Zeiss K A, Vonkeman H E, Voorn P
Department of Neurology, University of Rochester, School of Medicine and Dentistry, NY, USA.
Ann Neurol. 1995 Dec;38(6):852-61. doi: 10.1002/ana.410380605.
Preferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Terminals of preproenkephalin medium-size spiny neurons are more vulnerable than terminals of preprotachykinin neurons, but the peptidergic neurons of origin have not yet been shown to die preferentially. We sought to determine, in the striatum, whether preproenkephalin neurons were lost to a greater extent than preprotachykinin neurons and to determine whether there were decreases in specific messenger RNA (mRNA) levels of preproenkephalin, preprotachykinin, and calbindin D28k. We found a grade-related decrease in the number of preprotachykinin- and calbindin D28k-labeled neurons per measuring field in the caudate nucleus of patients with HD. Three measures of the neuronal level of preprotachykinin mRNA were all significantly reduced (6-65% of control values) in HD caudate nucleus. No decline in calbindin D28k mRNA levels per neuron were found in HD striata compared to control striata. We found a greater loss of preproenkephalin neurons per field than preprotachyknin neurons per field in the caudate nucleus of HD brains compared to control brains. Preprotachykinin neurons are lost in HD in a grade-related manner and surviving preprotachykinin neurons are impaired in function. However, preproenkephalin neurons are lost to a greater extent than preprotachykinin neurons, which may explain preferential changes found in projection regions of the striatum. Declines in neuropeptide mRNA may be specific in HD, since calbindin D28k mRNA levels were unchanged. Alterations in the levels of expression of preproenkephalin and preprotachykinin mRNA may be direct or indirect effects of the HD mutation.
亨廷顿舞蹈病（HD）中基底神经节神经元及其终末会出现选择性缺失。脑啡肽原中型多棘神经元的终末比速激肽原神经元的终末更易受损，但尚未证实产生肽能的神经元会优先死亡。我们试图确定，在纹状体中，脑啡肽原神经元的损失是否比速激肽原神经元更严重，并确定脑啡肽原、速激肽原和钙结合蛋白D28k的特定信使核糖核酸（mRNA）水平是否降低。我们发现，HD患者尾状核中每个测量视野内速激肽原和钙结合蛋白D28k标记的神经元数量呈等级相关减少。HD尾状核中速激肽原mRNA的三个神经元水平测量指标均显著降低（为对照值的6 - 65%）。与对照纹状体相比，HD纹状体中未发现单个神经元的钙结合蛋白D28k mRNA水平下降。与对照脑相比，我们发现HD脑尾状核中每个视野内脑啡肽原神经元的损失比速激肽原神经元更大。速激肽原神经元在HD中呈等级相关方式丢失，存活的速激肽原神经元功能受损。然而，脑啡肽原神经元的损失比速激肽原神经元更严重，这可能解释了在纹状体投射区域发现的选择性变化。神经肽mRNA的下降在HD中可能具有特异性，因为钙结合蛋白D28k mRNA水平未变。脑啡肽原和速激肽原mRNA表达水平的改变可能是HD突变的直接或间接影响。
