Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, China.
Medical Primate Research Center & Neuroscience Center, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Appl Biochem Biotechnol. 2021 Oct;193(10):3187-3201. doi: 10.1007/s12010-021-03586-w. Epub 2021 Jun 7.
Previous studies have shown that abnormal aggregation of alpha-synuclein (α-syn) protein is a major trigger of neurodegenerative diseases. The expression level of α-syn in different brain regions and the disease-susceptible regions varies with the development of the disease. The expression pattern of the α-syn protein in mouse brain has been precisely described in the literature. Some studies have also reported the ubiquitous expression of the α-syn protein in the central and peripheral in nonhuman primates (NHPs). However, little is known about the expression pattern of α-syn in the brain or in the primary organs of NHPs. Here, we investigated the expression profile of α-syn in different brain regions and the primary organs of NHPs. The α-syn protein was mainly distributed in layers III and V of the cerebral cortex and the hippocampus. In addition, strong immunofluorescent signals were detected in the striatum and the substantia nigra, especially in the globus pallidus and the substantia nigra pars compacta, where the expression was significantly and particularly strong, compared with that in the cerebellum or the cortex. In the cerebellum, intense α-syn signal was observed in the molecular layer, where it was significantly higher than in the nucleus or the medulla. In the brain, the α-syn was always detected both in the cytoplasm and the synapses. Additionally, the α-syn was widely expressed in primary organs. The α-syn signal was higher in the liver and small intestine than in the spleen. Thus, the regions displaying the highest α-syn expression are also those affected during the progression of neurodegenerative diseases. These results may provide basic reference data for the study of multi-systemic mechanism of neurodegenerative diseases.
先前的研究表明,α-突触核蛋白(α-syn)的异常聚集是神经退行性疾病的主要诱因。α-syn 在不同脑区和疾病易感区的表达水平随疾病的发展而变化。α-syn 蛋白在小鼠脑中的表达模式在文献中有精确描述。一些研究还报道了α-syn 蛋白在非人灵长类动物(NHPs)中枢和外周的普遍表达。然而,人们对α-syn 在 NHPs 大脑或主要器官中的表达模式知之甚少。在这里,我们研究了α-syn 在不同脑区和 NHPs 主要器官中的表达谱。α-syn 蛋白主要分布在大脑皮层的 III 层和 V 层以及海马体。此外,在纹状体和黑质中检测到强烈的免疫荧光信号,特别是在苍白球和黑质致密部,与小脑或皮层相比,其表达明显且特别强烈。在小脑,分子层观察到强烈的α-syn 信号,其强度明显高于核或髓质。在大脑中,α-syn 总是在细胞质和突触中被检测到。此外,α-syn 在主要器官中广泛表达。α-syn 信号在肝脏和小肠中高于脾脏。因此,显示最高α-syn 表达的区域也是神经退行性疾病进展过程中受影响的区域。这些结果可能为神经退行性疾病多系统机制的研究提供基本的参考数据。