Fusco F R, Chen Q, Lamoreaux W J, Figueredo-Cardenas G, Jiao Y, Coffman J A, Surmeier D J, Honig M G, Carlock L R, Reiner A
Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee-Memphis, The Health Sciences Center, Memphis, Tennessee 38163, USA.
J Neurosci. 1999 Feb 15;19(4):1189-202. doi: 10.1523/JNEUROSCI.19-04-01189.1999.
Immunohistochemistry and single-cell RT-PCR were used to characterize the localization of huntingtin and/or its mRNA in the major types of striatal neurons and in corticostriatal projection neurons in rats. Single-label immunohistochemical studies revealed that striatum contains scattered large neurons rich in huntingtin and more numerous medium-sized neurons moderate in huntingtin. Double-label immunohistochemical studies showed that the large huntingtin-rich striatal neurons include nearly all cholinergic interneurons and some parvalbuminergic interneurons. Somatostatinergic striatal interneurons, which are medium in size, rarely contained huntingtin. Calbindin immunolabeling showed that the vast majority of the medium-sized striatal neurons that contain huntingtin are projection neurons, but only approximately 65% of calbindin-labeled projection neurons (localized to the matrix compartment of striatum) were labeled for huntingtin. Calbindin-containing projection neurons of the matrix compartment and calbindin-negative projection neurons of the striatal patch compartment contained huntingtin with comparable frequency. Single-cell RT-PCR confirmed that striatal cholinergic interneurons contain huntingtin, but only approximately 65% of projection neurons contained detectable huntingtin message. The finding that huntingtin is not consistently found in striatal projection neurons [which die in Huntington's disease (HD)] but is abundant in striatal cholinergic interneurons (which survive in Huntington's disease) suggests that the mutation in huntingtin that causes HD may not directly kill neurons. In contrast to the heterogeneous expression of huntingtin in the different striatal neuron types, we found all corticostriatal neurons to be rich in huntingtin protein and mRNA. One possibility raised by our findings is that the HD mutation may render corticostriatal neurons destructive rather than render striatal neurons vulnerable.
免疫组织化学和单细胞逆转录聚合酶链反应被用于鉴定大鼠纹状体主要神经元类型以及皮质纹状体投射神经元中亨廷顿蛋白及其信使核糖核酸（mRNA）的定位。单标记免疫组织化学研究显示，纹状体含有散在的富含亨廷顿蛋白的大神经元以及数量更多、亨廷顿蛋白含量中等的中型神经元。双标记免疫组织化学研究表明，富含亨廷顿蛋白的大纹状体神经元几乎包括所有胆碱能中间神经元和一些小白蛋白能中间神经元。中等大小的生长抑素能纹状体中间神经元很少含有亨廷顿蛋白。钙结合蛋白免疫标记显示，绝大多数含有亨廷顿蛋白的中型纹状体神经元是投射神经元，但仅约65%的钙结合蛋白标记的投射神经元（定位于纹状体的基质区）被标记为含有亨廷顿蛋白。基质区含钙结合蛋白的投射神经元和纹状体斑块区钙结合蛋白阴性的投射神经元含有亨廷顿蛋白的频率相当。单细胞逆转录聚合酶链反应证实，纹状体胆碱能中间神经元含有亨廷顿蛋白，但仅约65%的投射神经元含有可检测到的亨廷顿蛋白信息。亨廷顿蛋白并非始终存在于纹状体投射神经元（在亨廷顿病中死亡）中，但在纹状体胆碱能中间神经元（在亨廷顿病中存活）中含量丰富，这一发现表明，导致亨廷顿病的亨廷顿蛋白突变可能不会直接杀死神经元。与亨廷顿蛋白在不同纹状体神经元类型中的异质性表达相反，我们发现所有皮质纹状体神经元都富含亨廷顿蛋白和mRNA。我们的研究结果提出的一种可能性是，亨廷顿病突变可能使皮质纹状体神经元具有破坏性，而不是使纹状体神经元易受损伤。
