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Amphetamine-induced dopaminergic toxicity:

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Amphetamine-induced dopaminergic toxicity:
SubTitle
a single dose animal model of Parkinson's disease
TitleInfo (ID = T-2); (type = alternative)
Title
Single dose animal model of Parkinson's disease
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17505
Identifier
ETD_1340
Language
LanguageTerm (authority = ISO 639-3:2007)
English
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Toxicology
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Neurotoxic agents--Physiological effect
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Parkinson???s disease--Pathophysiology
Abstract
Parkinson's disease affects millions of people worldwide and is characterized by loss of dopaminergic neurons of the nigro-striatal pathway. Although many mechanisms have been postulated to account for the destruction of these cells, no clear cause has been elucidated. The hypothesis that oxidative stress plays an important role in dopamine depletion in Parkinson's disease was examined through use of amphetamine, a dopaminergic toxicant known to act through oxidative stress. First, a thorough characterization of a single high dose of amphetamine was completed as a new model of Parkinson's disease. Then, antioxidant and anti-inflammatory treatments were used to protect against amphetamine's neurotoxic effects. The antioxidant ascorbic acid was successful in attenuating amphetamine-induced dopamine depletion, while others tested, including Trolox and EGCG, did not attenuate dopaminergic toxicity. In addition, an end product of lipid peroxidation, malondialdehyde, was measured in response to amphetamine treatment and evaluated with the time course of amphetamine-induced dopamine depletion. Studies have shown increased levels of malondialdehyde in the blood and brains of Parkinson's patients.
Finally, the behavior and sensitivity of mice with selective deletions of genes coding for GSTM1, PAK5, PAK6, or both PAK5 and PAK6 to amphetamine was examined. Multiple genes have been implicated in the etiology of Parkinson's disease, some of which may be associated with oxidative stress response, mitochondrial function, protein kinase function and/or neuronal survival mechanisms. A null mutation in GSTM1 has been associated with Parkinson's disease and plays a role as an antioxidant in the brain. Mice lacking the GSTM1 gene did not show an abnormal behavioral phenotype compared to controls and were not sensitive to amphetamine toxicity. The p21-activated kinases (PAKs) are highly expressed in the brain as well and have been implicated in several neurological disorders, including Parkinson's disease. Mice lacking one or more of the PAK genes showed motoric similarities to Parkinson's disease, although they were relatively resistant to amphetamine toxicity. Collectively, these experiments explored the role of oxidative stress, antioxidant function and related genetic components in a single dose, amphetamine animal model of Parkinson's disease.
PhysicalDescription
Extent
xiii, 267 pages
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application/pdf
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Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references (p. 253-266).
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Jobes
NamePart (type = given)
Michelle L.
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author
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Michelle L. Jobes
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Wagner
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George
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chair
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Advisory Committee
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George C Wagner
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Reuhl
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Kenneth
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internal member
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Advisory Committee
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Kenneth R Reuhl
Name (ID = NAME-4); (type = personal)
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Kusnecov
NamePart (type = given)
Alexander
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internal member
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Advisory Committee
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Alexander W Kusnecov
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Thiruchelvam
NamePart (type = given)
Mona
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RoleTerm (authority = RULIB)
internal member
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Advisory Committee
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Mona Thiruchelvam
Name (ID = NAME-6); (type = personal)
NamePart (type = family)
Halladay
NamePart (type = given)
Alycia
Role
RoleTerm (authority = RULIB)
outside member
Affiliation
Advisory Committee
DisplayForm
Alycia K Halladay
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2008
DateOther (qualifier = exact); (type = degree)
2008-10
Location
PhysicalLocation (authority = marcorg)
NjNbRU
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier (type = doi)
doi:10.7282/T3WS8TKP
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
AssociatedEntity (AUTHORITY = rulib); (ID = 1)
Name
Michelle Jobes
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
RightsEvent (AUTHORITY = rulib); (ID = 1)
Type
Permission or license
Detail
Non-exclusive ETD license
AssociatedObject (AUTHORITY = rulib); (ID = 1)
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License
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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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