Description
TitleMaternal T cell immune activation and postnatal stress
Date Created2016
Other Date2016-05 (degree)
Extent1 online resource (vi, 56 p. : ill.)
DescriptionPrenatal maternal immune activation (MIA) is a risk factor for several psychopathologic disorders, including bipolar disorder, autism, and schizophrenia. Most research has focused on using toll-like receptor agonists such as lipopolysaccharide or the synthetic viral genome analogue polyinosinic:polycytidylic acid as experimental immune activators. Little is known about how T cells, necessary for successful clearance of viruses and bacteria, may influence the neurodevelopment of the gestating fetus. Additionally, MIA has been implicated as the first hit in a two-hit hypothesis of schizophrenia development when coupled with a secondary insult, such as psychological stress, during adolescent neurodevelopment. To this end, I challenged pregnant C57BL/6J mice on day E12.5 of gestation with 200ug/kg of purified staphylococcal enterotoxin A (SEA), a potent superantigen, to oligoclonally activate maternal T cells. After birth, both male and female offspring were randomized into “stress” or “no stress” groups, where “stress” animals would experience a 14 day battery of mild, unpredictable stressors. All animals were then tested for spatial navigation in a water radial arm maze (wRAM), anxiety-like behavior in the elevated plus maze (EPM) and open-field, and sensorimotor gating, as measured by prepulse inhibition (PPI). In the wRAM, during hidden platform training, SEA-No Stress animals took significantly longer to find the escape platform and traveled significantly farther before finding it. SEA-No Stress animals also had a significantly higher number of fail errors, where they did not find the platform within 60 seconds. When testing for spatial memory, SEA-Stress animals spent the least amount of time in the platform arm, as well as taking significantly longer to make first entry. Stressed animals traveled further total distance in both the EPM and open field. Animals from SEA treated mothers spent less time investigating a novel object in the open field, as well as spent more time on the perimeter of the maze. No differences were observed between animals in PPI. Together, these findings suggest that specific T cell activation during pregnancy alters behavioral development in the offspring. Additionally, adolescent stress does not have an additive effect on prenatal SEA treatment, but rather combines to form a unique phenotype.
NoteM.S.
NoteIncludes bibliographical references
Noteby Nicholas W. Fox
Genretheses, ETD graduate
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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