Article ; Online: Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.
2014 Volume 3, Issue 5, Page(s) 725–734
Abstract: A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain ... ...
| Abstract | A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. |
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| MeSH term(s) | Animals ; Animals, Newborn ; Autistic Disorder/immunology ; Blotting, Western ; Brain/immunology ; Brain/metabolism ; Brain/pathology ; Cell Proliferation ; Cells, Cultured ; Female ; Grooming ; Inflammation/chemically induced ; Inflammation/immunology ; Inflammation/physiopathology ; Lipopolysaccharides/immunology ; Lipopolysaccharides/toxicity ; Male ; Maze Learning ; Mice ; Microglia/immunology ; NADPH Oxidases/immunology ; NADPH Oxidases/metabolism ; Oxidation-Reduction ; Phosphatidylinositol 3-Kinases/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/immunology ; Prenatal Exposure Delayed Effects/physiopathology ; Reactive Oxygen Species/immunology ; Reactive Oxygen Species/metabolism ; Signal Transduction/immunology ; Stem Cells/immunology |
| Chemical Substances | Lipopolysaccharides ; Reactive Oxygen Species ; NADPH Oxidases (EC 1.6.3.-) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) |
| Language | English |
| Publishing date | 2014-11-11 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2720528-9 |
| ISSN | 2213-6711 ; 2213-6711 |
| ISSN (online) | 2213-6711 |
| ISSN | 2213-6711 |
| DOI | 10.1016/j.stemcr.2014.09.004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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