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Behavioral, neurochemical, and neuroimmune changes in Nrf2 knockout mice following early postnatal exposure to valproic acid
Descriptive
TitleInfo
Title
Behavioral, neurochemical, and neuroimmune changes in Nrf2 knockout mice following early postnatal exposure to valproic acid
Name
(type = personal)
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(type = family)
Furnari
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Melody A.
NamePart
(type = date)
1987-
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Melody Furnari
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author
Name
(type = personal)
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(type = family)
Wagner
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(type = given)
George C
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George C Wagner
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Advisory Committee
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chair
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(type = family)
Kusnecov
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Alexander
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Alexander Kusnecov
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Advisory Committee
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internal member
Name
(type = personal)
NamePart
(type = family)
Iba
NamePart
(type = given)
M. Marcel
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M. Marcel Iba
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
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(type = personal)
NamePart
(type = family)
Reuhl
NamePart
(type = given)
Kenneth
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Kenneth Reuhl
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
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(type = family)
KONG
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(type = given)
AH-NG
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AH-NG KONG
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Advisory Committee
Role
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(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
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(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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school
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Text
Genre
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theses
OriginInfo
DateCreated
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2013
DateOther
(qualifier = exact);
(type = degree)
2013-05
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
In the present study, two agents known to exert neurotoxic effects through the generation of reactive oxygen species were administered to genetically-altered mice lacking the Nrf2 gene. Nrf2 is a transcription factor that induces genes that protect against oxidative stress and Nrf2 knockout mice have been shown to be more sensitive to oxidative stress. The first agent, valproic acid, is a GABA (gamma amino butyric acid) agonist known to cause behavioral deficits and damage to the hippocampus and cerebellum in rodents when administered on postnatal day 14, a time when behavioral skills are first maturing. The second, amphetamine, is a stimulant that induces dopamine release leading to oxidative stress with long-term effects of dopamine depletion and cell death. In prior studies, it was shown that early exposure to one toxicant leads to increased sensitivity to other toxicants. Accordingly, in these studies, Nrf2 knockout mice were exposed to valproic acid early in life and treated with amphetamine as adults. It was found that Nrf2 knockout mice were more sensitive to the toxic effects of valproic acid in development as seen through the open field activity test, rotorod, and Morris water maze. In addition, valproic acid-treated mice were found to be less social in the social chambers during adulthood. No differences were found in dopamine depletion between genotypes and postnatal day 14 pretreatment; all mice exposed to amphetamine had lower concentrations of dopamine compared to saline-treated counterparts. In conclusion, it appears that Nrf2 knockout mice are more sensitive to the behavioral toxicity cause by valproic acid during development but did not show enhanced sensitivity to amphetamine as adults. The Nrf2 knockout mice appear to be an excellent model to assess the effects of oxidative stress inducing neurotoxicants on behavioral development.
Subject
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Topic
Toxicology
RelatedItem
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Title
Rutgers University Electronic Theses and Dissertations
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Identifier
ETD_4613
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electronic resource
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application/pdf
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text/xml
Extent
viii, 167 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Melody A. Furnari
Subject
(authority = ETD-LCSH)
Topic
Transcription factors
Subject
(authority = ETD-LCSH)
Topic
Mice as laboratory animals
Subject
(authority = ETD-LCSH)
Topic
Transgenic mice
Subject
(authority = ETD-LCSH)
Topic
Toxicology--Animal models
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000068856
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T39S1PN0
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Furnari
GivenName
Melody
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2013-04-10 08:55:06
AssociatedEntity
Name
Melody Furnari
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
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windows xp
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