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GFAP expression and social deficits in transgenic mice overexpressing human sAPPα
Author(s) -
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
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22544
Subject(s) - gliosis , glial fibrillary acidic protein , genetically modified mouse , autism , biology , astrogliosis , neuroprotection , endocrinology , transgene , neurogenesis , neuroscience , medicine , immunology , immunohistochemistry , central nervous system , psychology , genetics , psychiatry , gene
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.