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The effects of methylmercuric chloride exposure on immediate early gene induction in the murine brain

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TitleInfo (displayLabel = Citation Title); (type = uniform)
Title
The effects of methylmercuric chloride exposure on immediate early gene induction in the murine brain
Name (ID = NAME001); (type = personal)
NamePart (type = family)
Cooper
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Joel F.
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Joel F. Cooper
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author
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Kusnecov
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Alexander
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Advisory Committee
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Alexander W. Kusnecov
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chair
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Reuhl
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Kenneth
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Advisory Committee
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Kenneth Reuhl
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internal member
Name (ID = NAME004); (type = personal)
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Wagner
NamePart (type = given)
George
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Advisory Committee
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George Wagner
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internal member
Name (ID = NAME005); (type = personal)
NamePart (type = family)
Zhou
NamePart (type = given)
Renping
Affiliation
Advisory Committee
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Renping Zhou
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internal member
Name (ID = NAME006); (type = personal)
NamePart (type = family)
Shi
NamePart (type = given)
Yufang
Affiliation
Advisory Committee
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Yufang Shi
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internal member
Name (ID = NAME007); (type = corporate)
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
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Graduate School - New Brunswick
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theses
OriginInfo
DateCreated (qualifier = exact)
2008
DateOther (qualifier = exact); (type = degree)
2008-05
Language
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English
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electronic
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application/pdf
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text/xml
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xv, 204 pages
Abstract
The present set of experiments was designed to examine the effects of dose, route of administration, and frequency of MeHg exposure on activation of neural stress nuclei, altered behavior in the open field and splenic cytokine production. MeHg exposure is associated with gross neuropathological alterations, behavioral deficits, and suppressed function of the immune system. Results from these experiments show that acute IP and ICV exposure of C57BL6J mice to MeHg results in increased recruitment of stress-associated nuclei, as measured by c-Fos immunoreactivity. Acute IP MeHg administration also causes dose-dependent decreases in exploratory behavior. Peripheral stimulation of the gastrointestinal vagus nerve by acute doses of MeHg could be responsible for stimulation of brainstem nuclei and activation of central stress nuclei, as peripheral exposure to LPS in vagotomized mice results in attenuated c-Fos response in limbic and autonomic regions of the murine brain. Proposed malaise-induced alterations in exploratory behavior may also be linked to vagal activation. In Experiment 2, multiple exposures to MeHg resulted in activation of fewer neural stress nuclei and attenuation of the dose-dependent effects of MeHg on open field behavior noted in Experiment 1. Repeated MeHg treatment followed by exposure to LPS resulted in a significantly increased c-Fos response, demonstrating that the reduction in c-Fos noted in response to repeated MeHg was not due to altered protein synthesis, but more likely due to habituated effects on neurotransmission. The splenic cytokine response to acute MeHg did not significantly affect proinflammatory cytokine production, but did increase IL-2; an effect that could have resulted from T-cell proliferation. Repeated exposure to MeHg increased splenic TNF- α, IL-6 and IL-10 levels, through unknown mechanisms. However, the spleen, which functions to both monitor the circulatory system for immunological stimuli and is the central site for the reticuloendothelial immune system, could be increasing cytokine production through macrophage-induced T-cell activation. Methylmercury has been shown in this thesis to uniquely activate stress-associated nuclei in the murine brain, inhibit exploratory behavior in the open field and increase splenic cytokine production likely due to its documented effects on both the nervous and immune systems.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references (p. 171-202).
Subject (ID = SUBJ1); (authority = RUETD)
Topic
Toxicology
Subject (ID = SUBJ2); (authority = ETD-LCSH)
Topic
Methylmercury--Physiological effect
Subject (ID = SUBJ3); (authority = ETD-LCSH)
Topic
Mice
Subject (ID = SUBJ4); (authority = ETD-LCSH)
Topic
Mice--Effects of chemicals on
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17292
Identifier
ETD_842
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3BZ66CJ
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
Copyright
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Copyright protected
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Open
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Name
Joel Cooper
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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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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