Regional and Cellular Mapping of Sortilin Immunoreactivity in Adult Human Brain
Regional and Cellular Mapping of Sortilin Immunoreactivity in Adult Human Brain
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成人大脑中分拣蛋白免疫反应性的区域和细胞图谱
DOI：
10.3389/fnana.2019.00031
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发表时间：
2019-03
影响因子：
2.9
通讯作者：
Yan Xiao Xin
中科院分区：
文献类型：
--
作者：
Xu Shu Yin;Zhang Qi Lei;Zhang Qi;Wan Lily;Jiang Juan;Tu Tian;Manavis Jim;Pan Aihua;Cai Yan;Yan Xiao Xin
分拣蛋白是液泡蛋白分拣10蛋白（VPS 10 P）结构域受体家族的成员，其在细胞中进行信号转导和蛋白质转运。分拣蛋白是神经降压素的第三种G蛋白非偶联受体，可以调节各种脑功能。最近的数据表明分拣蛋白参与情绪障碍、痴呆和阿尔茨海默型神经病理学。然而，迄今为止，关于人脑中分拣蛋白的区域和细胞表达的正常模式的数据不可用。使用无神经病理学的成年人死后大脑，目前的研究确定了整个大脑的分拣蛋白免疫反应性（IR）。Sortilin IR广泛存在于大脑和皮质下结构中，定位于体树突隔室中的神经元，但不定位于胶质细胞。在大脑中，sortilin IR表现出不同的区域和层状模式，与锥体，多极和多形神经元在皮质层II-VI，海马结构和杏仁复合体相对于GABA能中间神经元更明显的标记。在纹状体和丘脑中，许多小到中等大小的神经元显示轻IR，少数大尺寸神经元被重标记。在中脑和脑干中，sortilin IR在下行和上行神经解剖通路的中继中心的神经元中是不同的。免疫荧光双标显示，黑质多巴胺能神经元、Meynert基底核胆碱能神经元和蓝斑去甲肾上腺素能神经元共表达sortilin IR。相比之下，sortilin IR在嗅球和小脑皮质中较弱，二尖瓣和浦肯野细胞几乎不可见。在杏仁复合体的外侧，基底外侧和基底内侧核，以及皮质层II-VI，这建立了标记的神经元之间的体大小和分拣蛋白IR的强度之间的正相关性进行了定量分析。总之，本研究证明了分拣蛋白在人脑中的主要神经元表达具有显著的区域和细胞类型变异性。分拣蛋白在锥体神经元、多巴胺能神经元、去甲肾上腺素能神经元和胆碱能神经元中的富集表达表明，这种蛋白质可能是相对较大的投射神经元群体中的信号转导、蛋白质运输和代谢稳态特别需要的。
Sortilin is a member of the vacuolar protein sorting 10 protein (VPS10P) domain receptor family, which carries out signal transduction and protein transport in cells. Sortilin serves as the third, G-protein uncoupled, receptor of neurotensin that can modulate various brain functions. More recent data indicate an involvement of sortilin in mood disorders, dementia and Alzheimer-type neuropathology. However, data regarding the normal pattern of regional and cellular expression of sortilin in the human brain are not available to date. Using postmortem adult human brains free of neuropathology, the current study determined sortilin immunoreactivity (IR) across the entire brain. Sortilin IR was broadly present in the cerebrum and subcortical structures, localizing to neurons in the somatodendritic compartment, but not to glial cells. In the cerebrum, sortilin IR exhibited differential regional and laminar patterns, with pyramidal, multipolar and polymorphic neurons in cortical layers II–VI, hippocampal formation and amygdaloid complex more distinctly labeled relative to GABAergic interneurons. In the striatum and thalamus, numerous small-to-medium sized neurons showed light IR, with a small group of large sized neurons heavily labeled. In the midbrain and brainstem, sortilin IR was distinct in neurons at the relay centers of descending and ascending neuroanatomical pathways. Dopaminergic neurons in the substantia nigra, cholinergic neurons in the basal nuclei of Meynert and noradrenergic neurons in the locus coeruleus co-expressed strong sortilin IR in double immunofluorescence. In comparison, sortilin IR was weak in the olfactory bulb and cerebellar cortex, with the mitral and Purkinje cells barely visualized. A quantitative analysis was carried out in the lateral, basolateral, and basomedial nuclei of the amygdaloid complex, as well as cortical layers II–VI, which established a positive correlation between the somal size and the intensity of sortilin IR among labeled neurons. Together, the present study demonstrates a predominantly neuronal expression of sortilin in the human brain with substantial regional and cell-type variability. The enriched expression of sortilin in pyramidal, dopaminergic, noradrenergic and cholinergic neurons suggests that this protein may be particularly required for signal transduction, protein trafficking and metabolic homeostasis in populations of relatively large-sized projective neurons.
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影响因子：
5
作者：
Tyler-McMahon, BM;Stewart, JA;Richelson, E
通讯作者：
Richelson, E
影响因子：
4.2
作者：
Allard, Simon;Jacobs, Marie L.;Cuello, A. Claudio
通讯作者：
Cuello, A. Claudio
DOI：
10.1177/27.10.512327
发表时间：
1979-10
期刊：
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
影响因子：
--
作者：
J. Polak;S. Bloom
通讯作者：
J. Polak;S. Bloom
影响因子：
5.6
作者：
Moreno S;Devader CM;Pietri M;Borsotto M;Heurteaux C;Mazella J
通讯作者：
Mazella J
分拣蛋白碎片沉积在人类大脑的老年斑块上
影响因子：
2.9
作者：
Hu X;Hu ZL;Li Z;Ruan CS;Qiu WY;Pan A;Li CQ;Cai Y;Shen L;Chu Y;Tang BS;Cai H;Zhou XF;Ma C;Yan XX
通讯作者：
Yan XX