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Publication Date

Summer 2015

Degree Type

Thesis - Campus Access Only

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Tzvia Abramson

Keywords

Gabrb3, gene-environment, LPS, Maternal immune activation, Neural progenitor cells, Poly I:C

Subject Areas

Biology; Neurosciences; Developmental biology

Abstract

Autism spectrum disorder (ASD) is a group of neuro-developmental disorders characterized by social communication deficits and repetitive behaviors. ASD is believed to be caused by a number of genetic and environmental risk factors and complex interactions between them. Human clinical studies have shown an association between bacterial and viral infections in pregnant women during the first and second trimesters and ASD in their offspring. In addition, studies using animal models have linked an inflammatory state in the mother to ASD-relevant behaviors in the offspring, but the molecular mechanisms mediating the influence of these prenatal risk factors on behavior are unknown. To understand the acute effects of maternal immune activation (MIA) on embryonic neurobiological abnormalities, we administered bacterial mimetic lipopolysaccharide (LPS) and viral mimetic poly inosinic: cytidilic acid (Poly I:C) during mid-gestation in pregnant mice. In this period, the placenta, though vulnerable to environmental insults, allows for most fetuses to survive to term and for cortical neurogenesis to actively occur in the fetal brain. Twenty four hours after LPS and Poly I:C administration, we observed defects in neocortical neural progenitor proliferation and apical cytoarchitecture, differentiation and lineage specification. We also report variations in responses to LPS and Poly I:C, suggesting a differential vulnerability. Finally, we show a unique gene - environment interaction study with MIA and Gabrb3, one of the genes implicated in ASD, leading to synergistic adverse effects on pregnancy.

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