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Mechanisms of the neural and behavioral effects of staphylococcal enterotoxin A after acute and repeated exposure
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Text
TitleInfo
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Title
Mechanisms of the neural and behavioral effects of staphylococcal enterotoxin A after acute and repeated exposure
SubTitle
the role of tumor necrosis factor-alpha
Identifier
ETD_1425
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051102
Language
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eng
Genre
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theses
Subject
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(authority = RUETD)
Topic
Toxicology
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Staphylococcus
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Tumor necrosis factor
Abstract
Superantigens (SAgs) activate the immune system by stimulating excessive proliferation of T cells, resulting in the release of cytokines such as tumor necrosis factor-alpha (TNFα). As an adaptive feedback mechanism, SAgs can also activate the hypothalamic pituitary adrenal (HPA) axis by stimulating the release of corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropic hormone (ACTH) from the anterior pituitary, and ultimately corticosterone (CORT) from the adrenal gland. Behavioral consequences of SAg activation include increased gustatory neophobia, neophobia to inanimate non-gustatory objects, and heightened anxiety. Cytokines such as TNFα have been shown to mediate some of these behavioral consequences as well as the endocrine and neurobiological effects of SAg exposure.
The present experiments were designed to determine the role of TNF receptor I (TNFRI) and TNF receptor II (TNFRII) in mediating the effects of acute and repeated SEA. First, the in vivo repercussions of repeated stimulation with SEA were assessed. Then TNFRI- and TNFRII-deficient animals were tested several hours after acute and secondary exposure to SEA, as well as several days after acute SEA exposure. These studies showed that TNFRI was important in mediating the anorexia and CORT response following acute SEA exposure, but not the increase in neophobia several days following exposure. In addition, TNFRI was also important in mediating the endocrine effects of repeated SEA.
Since TNFα was shown to regulate the endocrine effects of SEA, a set of experiments also confirmed that glucocorticoids play an important role in regulating TNFα tolerance following secondary SEA exposure. In addition, the consequences of glucocorticoid disruption on the effects of acute and repeated challenge with SEA were determined through the use of chronic restraint. The results showed that chronic restraint produced an overall increase in interleukin-10 (IL-10) and a blunted interleukin-2 (IL-2) response following immediate acute SEA exposure. However, when the acute exposure was given more distal to the end of restraint period there was an enhanced IL-2 and TNFα response following acute, but not secondary SEA exposure. Collectively, these studies demonstrate the reciprocal effect of TNFα and glucocorticoids after acute and repeated SEA exposure.
The present experiments were designed to determine the role of TNF receptor I (TNFRI) and TNF receptor II (TNFRII) in mediating the effects of acute and repeated SEA. First, the in vivo repercussions of repeated stimulation with SEA were assessed. Then TNFRI- and TNFRII-deficient animals were tested several hours after acute and secondary exposure to SEA, as well as several days after acute SEA exposure. These studies showed that TNFRI was important in mediating the anorexia and CORT response following acute SEA exposure, but not the increase in neophobia several days following exposure. In addition, TNFRI was also important in mediating the endocrine effects of repeated SEA.
Since TNFα was shown to regulate the endocrine effects of SEA, a set of experiments also confirmed that glucocorticoids play an important role in regulating TNFα tolerance following secondary SEA exposure. In addition, the consequences of glucocorticoid disruption on the effects of acute and repeated challenge with SEA were determined through the use of chronic restraint. The results showed that chronic restraint produced an overall increase in interleukin-10 (IL-10) and a blunted interleukin-2 (IL-2) response following immediate acute SEA exposure. However, when the acute exposure was given more distal to the end of restraint period there was an enhanced IL-2 and TNFα response following acute, but not secondary SEA exposure. Collectively, these studies demonstrate the reciprocal effect of TNFα and glucocorticoids after acute and repeated SEA exposure.
PhysicalDescription
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electronic resource
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xix, 278 p. : ill.
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Note
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Ph.D.
Note
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Includes bibliographical references (p. 158-173)
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by Daniella R. Urbach
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Urbach
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Daniella R.
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Daniella R. Urbach
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Reuhl
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Kenneth
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chair
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Advisory Committee
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Kenneth Reuhl
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(type = family)
Kusnecov
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Alexander
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internal member
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Advisory Committee
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Alexander Kusnecov
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Wagner
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George
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George Wagner
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Thiruchelvam
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Mona
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internal member
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Advisory Committee
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Mona Thiruchelvam
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Shi
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Yufang
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outside member
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Advisory Committee
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Yufang Shi
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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2009
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2009-01
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xx
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NjNbRU
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Rutgers University Electronic Theses and Dissertations
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ETD
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Identifier
(type = doi)
doi:10.7282/T3RR1ZF9
Genre
(authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
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Open
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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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