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Early life influences of pharmacological and immune stressors on development

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TitleInfo
Title
Early life influences of pharmacological and immune stressors on development
Name (type = personal)
NamePart (type = family)
Norton
NamePart (type = given)
Sara A.
NamePart (type = date)
1991-
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Sara A. Norton
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author
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Kusnecov
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Alexander
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Alexander Kusnecov
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Advisory Committee
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chair
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Wagner
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George
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George Wagner
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Advisory Committee
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internal member
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Zhang
NamePart (type = given)
Huaye
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Huaye Zhang
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Advisory Committee
Role
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internal member
Name (type = personal)
NamePart (type = family)
Samuels
NamePart (type = given)
Ben
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Ben Samuels
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Advisory Committee
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internal member
Name (type = personal)
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Ellman
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Lauren
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Lauren Ellman
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Advisory Committee
Role
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outside member
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
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School of Graduate Studies
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school
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Text
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theses
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2019-10
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2019
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2019
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English
Abstract (type = abstract)
Neurodevelopmental disorders manifest early and may impair function throughout life. Exposure to environmental challenges is thought to play a causal role in many such disorders, but a key unanswered question relates to the vulnerability window(s) during which there is an increased sensitivity to these challenges. In a mouse model, we found that administration of the GABAergic toxicant valproic acid (VPA) differentially disrupted neurobehavioral development depending on the precise timing of exposure, and that the resulting behavioral profiles were sex-dependent. Specifically, neonatal C57BL/6 mice were challenged with 400 mg/kg VPA or saline on postnatal day 14 (P14) or 300 mg/kg VPA or saline on postnatal day 7 (P7). Animals were then assessed on a battery of behavioral tests chosen to assess social, emotional, and cognitive functioning. While VPA exposure at P14 resulted in a behaviorally disinhibited phenotype in males, VPA exposure at P7 resulted in social abnormalities in females. In addition, a single VPA challenge at either P7 or P14 affected dendritic spine plasticity in brain regions thought to regulate behaviors that reflect impulsivity. Finally, the behavioral consequences of VPA challenge were compared with an immunogenic challenge using the T cell superantigen, staphylococcal enterotoxin A (SEA). Challenge with SEA at P7 and P14 revealed that interleukin-2 (IL-2) production was lacking at P7, but not P14. Therefore, behavior was investigated after P14 treatment. There were no major differences in social, emotional or cognitive behaviors between SEA- and saline-treated mice during adolescence or adulthood. Overall, this investigation revealed that pharmacological challenges that focus on disruption of the GABAergic system influenced neurodevelopment in a sex- and time-dependent manner. However, T cell immune challenge was less disruptive, possibly due to the absence of key neuromodulatory cytokines that are normally induced by SEA in adult rodents and by other proinflammatory stimuli that target non-T cell populations. In conclusion, identifying the approximate vulnerability windows during postnatal development may allow for a better understanding of underlying mechanisms resulting in toxicant-induced deficits and provide a focus for prevention efforts.
Subject (authority = RUETD)
Topic
Psychology
Subject (authority = local)
Topic
Neurodevelopmental disorders
Subject (authority = LCSH)
Topic
Newborn infants -- Development
Subject (authority = LCSH)
Topic
Newborn infants -- Effect of drugs on
Subject (authority = LCSH)
Topic
Neurobehavioral disorders
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
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ETD
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Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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ETD_10315
Identifier (type = doi)
doi:10.7282/t3-3fzj-0r84
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application/pdf
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text/xml
Extent
1 online resource (xi, 116 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
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Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
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Norton
GivenName
Sara
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-09-24 12:47:05
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Name
Sara Norton
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Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Type
Embargo
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2020-10-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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