RT Journal Article
T1 Maternal Inflammation Contributes to Brain Overgrowth and Autism- Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells.
A1 Le Belle, Janel E.
A1 Sperry, Jantzen
A1 Ngo, Amy
A1 Ghochani, Yasmin
A1 Laks, Dan R.
A1 López-Aranda, Manuel Francisco
A1 Silva, Alcino J.
A1 Kornblum, Harley I.
K1 Trastornos del espectro autista - Etiología
K1 Células madre neurales
K1 Inflamación (Patología)
K1 Embarazo
AB 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.
PB CellPress
YR 2014
FD 2014-11-11
LK https://hdl.handle.net/10630/39204
UL https://hdl.handle.net/10630/39204
LA eng
NO Le Belle JE, Sperry J, Ngo A, et al. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells. Stem Cell Reports. 2014;3(5):725-734. doi:10.1016/j.stemcr.2014.09.004
NO This work was supported by the following grants and awards: Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to H.I.K.); Cure Autism Now Fellowship (to J.E.L.); Autism Speaks Basic and Clinical grant (to H.I.K.); Autism Speaks Environmental Sciences grant (to J.E.L.); Center for Autism Research and Treatment (CART) Pilot Grant Award #06LEB2008, which is supported by NIH/NICHD grant P50-HD-055784 (to J.E.L.); and NIH grant MH65756 (to H.I.K.). Flow cytometry and cell sorting was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and the Center for AIDS Research Flow Cytometry Core Facility, which is supported by NIH awards CA-16042 and AI-28697, the JCCC, the UCLA AIDS Institute, the David Geffen School of Medicine at UCLA, and the UCLA Chancellor’s Office.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026