| First Author | Bailey AR | Year | 2013 |
| Journal | Glia | Volume | 61 |
| Issue | 9 | Pages | 1556-69 |
| PubMed ID | 23840007 | Mgi Jnum | J:199441 |
| Mgi Id | MGI:5502793 | Doi | 10.1002/glia.22544 |
| Citation | Bailey AR, et al. (2013) GFAP expression and social deficits in transgenic mice overexpressing human sAPPalpha. Glia 61(9):1556-69 |
| abstractText | Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPalpha), the product of alpha-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPalpha 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 sAPPalpha and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPalpha levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPalpha (TgsAPPalpha mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPalpha mice, and those derived from wild-type mice treated with sAPPalpha, displayed suppressed beta-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPalpha levels are observed in subsets of individuals with autism and TgsAPPalpha mice display signs suggestive of gliosis and behavioral impairment. |
