Expression of the Excitatory Postsynaptic Scaffolding Protein, Shank3, in Human Brain: Effect of Age and Alzheimer's Disease.
Expression of the Excitatory Postsynaptic Scaffolding Protein, Shank3, in Human Brain: Effect of Age and Alzheimer's Disease.
复制标题
DOI：
10.3389/fnagi.2021.717263
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Yan XX
中科院分区：
文献类型：
--
作者：
Wan L;Ai JQ;Yang C;Jiang J;Zhang QL;Luo ZH;Huang RJ;Tu T;Pan A;Tu E;Manavis J;Xiao B;Yan XX
Shank3是兴奋性突触的突触后支架蛋白。SHANK3的突变或变异与各种精神和神经疾病有关。我们试图确定其在人脑中的正常表达模式，以及其随年龄和阿尔茨海默病（AD）型β-淀粉样蛋白（Aβ）和Tau发病机制的变化（如果有的话）。总的来说，Shank3免疫反应性（IR）在很大程度上表现为神经细胞模式，在大脑区域间具有不同的层流/区域分布。在青少年和成人中，大脑、纹状体和丘脑中的锥体/多极神经元亚群表现为中度IR，而脑干中的一些大尺寸神经元和小脑皮层中的颗粒细胞表现为轻度IR。在双免疫荧光中，Shank3 IR发生在神经元体细胞和大树突的皮层下区域，与突触素标记的突触前终末相对。在老年病例中，免疫标记的神经元体减少，在AD病例中，齿状回分子层的神经标记被破坏。在免疫印迹中，Shank3蛋白水平与不同脑区突触后密度蛋白95 （PSD95）水平呈正相关。与青年组和成年组相比，老年和AD患者前额叶、中央前和小脑皮质溶物中Shank3、PSD95和突触素的免疫印迹水平降低。综上所述，脑结构/区域间Shank3表达的差异表明兴奋性突触的局部密度存在差异。在前脑亚区富集的Shank3表达似乎与该蛋白在高级认知功能调节中的作用不一致。其在老年和AD脑中的表达下降可能与兴奋性突触的退化有关。
Shank3 is a postsynaptic scaffolding protein of excitatory synapses. Mutations or variations of SHANK3 are associated with various psychiatric and neurological disorders. We set to determine its normal expression pattern in the human brain, and its change, if any, with age and Alzheimer’s disease (AD)-type β-amyloid (Aβ) and Tau pathogenesis. In general, Shank3 immunoreactivity (IR) exhibited largely a neuropil pattern with differential laminar/regional distribution across brain regions. In youth and adults, subsets of pyramidal/multipolar neurons in the cerebrum, striatum, and thalamus showed moderate IR, while some large-sized neurons in the brainstem and the granule cells in the cerebellar cortex exhibited light IR. In double immunofluorescence, Shank3 IR occurred at the sublemmal regions in neuronal somata and large dendrites, apposing to synaptophysin-labeled presynaptic terminals. In aged cases, immunolabeled neuronal somata were reduced, with disrupted neuropil labeling seen in the molecular layer of the dentate gyrus in AD cases. In immunoblot, levels of Shank3 protein were positively correlated with that of the postsynaptic density protein 95 (PSD95) among different brain regions. Levels of Shank3, PSD95, and synaptophysin immunoblotted in the prefrontal, precentral, and cerebellar cortical lysates were reduced in the aged and AD relative to youth and adult groups. Taken together, the differential Shank3 expression among brain structures/regions indicates the varied local density of the excitatory synapses. The enriched Shank3 expression in the forebrain subregions appears inconsistent with a role of this protein in the modulation of high cognitive functions. The decline of its expression in aged and AD brains may relate to the degeneration of excitatory synapses.
登录
查看更多内容
影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
影响因子：
4
作者：
Carbonell, Felix;Zijdenbos, Alex P.;Bedell, Barry J.
通讯作者：
Bedell, Barry J.
影响因子：
5.2
作者：
Boccuto, Luigi;Lauri, Maria;Schwartz, Charles E.
通讯作者：
Schwartz, Charles E.
影响因子：
0.9
作者：
Chen, Chia-Hsiang;Chen, Hsin-I;Gau, Susan Shur-Fen
通讯作者：
Gau, Susan Shur-Fen