Huntingtin immunoreactivity in the rat neostriatum: differential accumulation in projection and interneurons.
Huntingtin immunoreactivity in the rat neostriatum: differential accumulation in projection and interneurons.
复制标题
大鼠新纹状体中的亨廷顿蛋白免疫反应性：投射神经元和中间神经元中的差异积累。
DOI：
10.1006/exnr.1997.6441
复制
发表时间：
1997
影响因子：
5.3
通讯作者：
Standaert,DG
中科院分区：
文献类型：
--
作者：
Kosinski,CM;Cha,JH;Young,AB;Persichetti,F;MacDonald,M;Gusella,JF;PenneyJr,JB;Standaert,DG
亨廷顿氏病是由编码亨廷顿蛋白的基因突变引起的。人类疾病的特征，其特征在于选择性损失的神经元从新纹状体，可以复制啮齿动物的兴奋性毒素管理。在受影响的个体和啮齿动物模型中，纹状体投射神经元大量丢失，中间神经元选择性保留。此外，在人类疾病中，纹状体损伤的最早证据发现于纹状体的纹状体区域。已知编码亨廷顿蛋白的mRNA由整个脑的神经元表达，这种分布不能解释所观察到的神经元死亡的选择性模式。使用荧光免疫细胞化学和共聚焦显微镜与亨廷顿蛋白的抗体，我们已经观察到，在大鼠纹状体投射神经元的一个子集包含密集的亨廷顿蛋白免疫反应（HT-IR）的积累，而大多数神经元在纹状体中包含小得多的金额。如钙结合蛋白-D28 K染色所定义的，强烈染色的神经元集中在纹状体纹状体内。在基质区，相对较少的神经元含有密集的HT-IR的积累，这些细胞总是缺乏钙结合蛋白-D28 K的核周染色。纹状体中间神经元，通过胆碱乙酰转移酶、小清蛋白、钙视网膜蛋白或神经元型一氧化氮合酶的免疫反应性的存在来鉴定，表现出很少或没有HT-ir。纹状体中间神经元中HT-ir的缺乏，以及纹状体神经元亚群中染色的突出，反映了这些不同类型的细胞在人类亨廷顿病早期阶段和啮齿动物兴奋毒性模型中的选择性脆弱性。我们的观察结果表明，机制，调节亨廷顿蛋白的积累可能发挥核心作用，在神经元变性的亨廷顿病。
Huntington's disease is caused by a mutation of the gene encoding the protein huntingtin. Features of the human disease, characterized by selective loss of neurons from the neostriatum, can be replicated in rodents by administration of excitotoxins. In both affected individuals and the rodent model, there is massive loss of striatal projection neurons with selective sparing of interneurons. Furthermore, in the human disease the earliest evidence of striatal injury is found in striosomal regions of the striatum. The mRNA encoding huntingtin is known to be expressed by neurons throughout the brain, a distribution which does not account for the selective patterns of neuronal death which are observed. Using fluorescence immunocytochemistry and confocal microscopy with an antibody to huntingtin, we have observed that in rats a subset of striatal projection neurons contains dense accumulations of huntingtin immunoreactivity (HT-ir), while most neurons in the striatum contain much smaller amounts. The intensely stained neurons are concentrated within the striatal striosomes, as defined by calbindin-D28Kstaining. In the matrix regions, relatively few neurons contain dense accumulations of HT-ir, and these cells always lack perikaryal staining for calbindin-D28K. Striatal interneurons, identified by the presence of immunoreactivity for choline acetyltransferase, parvalbumin, calretinin, or neuronal nitric oxide synthase, exhibit little or no HT-ir. The paucity of HT-ir in striatal interneurons, as well as the prominence of staining in a subset of striosomal neurons, mirrors the selective vulnerability of these different types of cells in early stages of human Huntington's disease and in rodent excitotoxic models of the disorder. Our observations suggest that mechanisms which modulate the accumulation of huntingtin may play a central role in the neuronal degeneration of Huntington's disease.