CERVO Brain Research Center, Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, 2601, Chemin de la Canardière, Quebec City, QC, G1J 2G3, Canada.
Brain Struct Funct. 2021 Jul;226(6):1879-1891. doi: 10.1007/s00429-021-02298-5. Epub 2021 May 20.
Interneurons play a significant role in the functional organization of the striatum and some of them display marked plastic changes in dopamine-depleted conditions. Here, we applied immunohistochemistry on brain sections from 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease and sham animals to characterize the regional distribution and the morphological and neurochemical changes of striatal interneurons expressing the calcium-binding protein calretinin (CR). Two morphological subtypes of calretinin-immunostained (CR +) interneurons referred, respectively, as small- and medium-sized CR + interneurons were detected in 6-OHDA- and sham-lesioned animals. The small cells (9-12 µm) prevail in the anterior and dorsal striatal regions; they stain intensely for CR and display a single slightly varicose and moderately arborized process. The medium-sized CR + interneurons (15-20 µm) are more numerous than the small CR + cells and rather uniformly distributed within the striatum; they stain weakly for CR and display 2-3 long, slightly varicose and poorly branched dendrites. The density of medium CR + interneurons is significantly decreased in the dopamine-depleted striatum (158 ± 15 neurons/mm), when compared to sham animals (370 ± 41 neurons/mm), whereas that of the small-sized CR + interneurons is unchanged (174 ± 46 neurons/mm in 6-OHDA-lesioned striatum and 164 ± 22 neurons/mm in sham-lesioned striatum). The nucleus accumbens is populated only by medium-sized CR + interneurons, which are distributed equally among the core and shell compartments and whose density is unaltered after dopamine denervation. Our results provide the first evidence that the medium-sized striatal interneurons expressing low level of CR are specifically targeted by dopamine denervation, while the small and intensely immunoreactive CR + cells remain unaffected. These findings suggest that high expression of the calcium-binding protein CR might protect striatal interneurons against an increase in intracellular calcium level that is believed to arise from altered glutamate corticostriatal transmission in Parkinson's disease.
中间神经元在纹状体的功能组织中发挥着重要作用，其中一些在多巴胺耗竭的情况下表现出明显的可塑性变化。在这里，我们应用免疫组织化学方法对 6-羟多巴胺（6-OHDA）帕金森病小鼠模型和假手术动物的脑切片进行了研究，以描述表达钙结合蛋白 calretinin（CR）的纹状体中间神经元的区域性分布和形态及神经化学变化。在 6-OHDA 和假手术损伤的动物中，检测到两种形态学亚型的 calretinin 免疫染色（CR+）中间神经元，分别称为小和中 CR+ 中间神经元。小细胞（9-12μm）在前部和背侧纹状体区域占优势；它们强烈地染色为 CR，并显示单个略微迂曲和中度分枝的过程。中 CR+ 中间神经元（15-20μm）比小 CR+ 细胞多，并且在纹状体中均匀分布；它们对 CR 染色弱，并显示 2-3 个长的、略微迂曲和分枝不良的树突。在多巴胺耗竭的纹状体中，中 CR+ 中间神经元的密度显著降低（158±15 个/毫米），与假手术动物相比（370±41 个/毫米），而小 CR+ 中间神经元的密度不变（6-OHDA 损伤的纹状体中为 174±46 个/毫米，假手术损伤的纹状体中为 164±22 个/毫米）。伏隔核仅由中 CR+ 中间神经元组成，这些神经元均匀分布在核心和壳隔室中，并且在多巴胺去神经支配后其密度没有改变。我们的结果首次证明，表达低水平 CR 的中型纹状体中间神经元是多巴胺去神经支配的特异性靶点，而小而强烈免疫反应性的 CR+ 细胞不受影响。这些发现表明，钙结合蛋白 CR 的高表达可能保护纹状体中间神经元免受细胞内钙水平升高的影响，这种升高被认为是帕金森病中谷氨酸皮质纹状体传递改变引起的。
