GFAP expression and social deficits in transgenic mice overexpressing human sAPPα.
GFAP expression and social deficits in transgenic mice overexpressing human sAPPα.
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作者：
Bailey, Antoinette R.;Hou, Huayan;Song, Min;Obregon, Demian F.;Portis, Samantha;Barger, Steven;Shytle, Doug;Stock, Saundra;Mori, Takashi;Sanberg, Paul G.;Murphy, Tanya;Tan, Jun
自闭症患者表现出社交互动和语言障碍，以及受限制的、刻板的行为。在一些自闭症患者的血浆中，发现α-分泌酶裂解APP的产物-分泌淀粉样前体蛋白α (sAPPα)水平升高。sAPPα蛋白具有神经营养和神经保护作用，最近发现它通过IL-6途径与人神经干细胞（NSCs）的胶质细胞分化相关。考虑到死后自闭症大脑中神经胶质瘤的证据，我们假设自闭症患者的亚群会表现出中枢神经系统sAPPα的升高，而模拟这一观察的小鼠会显示出神经胶质瘤和自闭症样行为的标志物。与对照组相比，观察到自闭症患者大脑中sAPPα水平升高。过表达人sAPPα的转基因小鼠（TgsAPPα小鼠）表现出低活性、社交能力受损、脑胶质纤维酸性蛋白（GFAP）表达增加、Notch1和IL-6水平改变。从TgsAPPα小鼠和野生型小鼠中分离的NSCs均表现出β-微管蛋白III抑制和GFAP表达升高。这些结果表明，在自闭症个体亚群中观察到脑sAPPα水平升高，TgsAPPα小鼠表现出胶质细胞增生和行为障碍的迹象。
Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.
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影响因子：
14.5
作者：
Bailey, A;Luthert, P;Lantos, P
通讯作者：
Lantos, P
影响因子：
56.9
作者：
Bonni, A;Sun, Y;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1016/s0304-4165(02)00256-8
发表时间：
2002-07-03
影响因子：
3
作者：
Das, A;Smalheiser, NR;Kaplan, A
通讯作者：
Kaplan, A
影响因子：
4.7
作者：
Barger, SW;Basile, AS
通讯作者：
Basile, AS
影响因子：
2.9
作者：
Knauer, MF;Orlando, RA;Glabe, CG
通讯作者：
Glabe, CG