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Examination of the role of PTEN in ionotropic glutamate receptor expression

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TitleInfo
Title
Examination of the role of PTEN in ionotropic glutamate receptor expression
Name (type = personal)
NamePart (type = family)
Kazdoba-Leach
NamePart (type = given)
Tatiana
NamePart (type = date)
1978-
DisplayForm
Tatiana Kazdoba-Leach
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
D'Arcangelo
NamePart (type = given)
Gabriella
DisplayForm
Gabriella D'Arcangelo
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Firestein
NamePart (type = given)
Bonnie
DisplayForm
Bonnie Firestein
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
McGann
NamePart (type = given)
John
DisplayForm
John McGann
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Zheng
NamePart (type = given)
Steven
DisplayForm
Steven Zheng
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-01
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The phosphatase Pten negatively regulates PI3K/Akt/mTOR signaling, a pathway critical for cell growth and protein synthesis. Germline PTEN mutations are implicated in seizure and autism, suggesting that alterations in PTEN affect neuronal function and development. Several brain-specific conditional Pten knockout (KO) mice exhibit enlarged brains, neuronal hypertrophy and increased seizure susceptibility, which may be indicative of altered glutamate receptor function. mTOR inhibition can suppress seizure activity observed in these Pten mutant models, revealing the importance of mTOR signaling in Pten-dependent phenotypes. To better understand how Pten may regulate neuronal excitability, ionotropic glutamate receptor expression was examined in NEX-Pten homozygous KO mice, which lack Pten in nearly all forebrain excitatory neurons. Biochemical analyses revealed alterations in select NMDA and AMPA receptor subunit protein levels in the forebrains of newly born NEX-Pten KO mice, suggesting developmental loss of Pten can affect synaptic proteins important for neurotransmission. Similarly, initial analysis of CaMKIIα-Pten KO mice indicated postnatal loss of Pten in excitatory neurons may also alter NMDA receptor subunits in the cortex, but not the hippocampus, underscoring the importance of Pten for proper synaptic protein expression. To further characterize the effects of Pten deletion on glutamate receptor subunit expression, dissociated cortical neuronal cultures were used to evaluate how chronic Pten deficiency alters glutamate receptors over time. NMDA receptor abnormalities were modest and transient, indicating that alterations in glutamate receptor subunits may normalize due to homeostatic mechanisms. Further, pharmacological inhibition of PI3K reduced select NMDA receptor subunits in dissociated cortical cultures. Together, these data suggest that in vivo activation of PI3K through loss of Pten leads to selective increases in NMDA receptor subunits in cortical neurons, but not hippocampal neurons, since no alterations were detected in this region. Additional studies with rapamycin and second generation mTOR inhibitors are required to determine how mTOR function contributes to the glutamate receptor phenotype. The NEX-Pten model demonstrates that Pten may be crucial in controlling neuronal excitability at the synapse. Dysregulation of these functions may underlie some of the phenotypes associated with PTEN mutations in the human population.
Subject (authority = RUETD)
Topic
Neuroscience
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5217
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xi, 124 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Tatiana Maria Kazdoba-Leach
Subject (authority = ETD-LCSH)
Topic
Phosphatases
Subject (authority = ETD-LCSH)
Topic
Neurochemistry
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3N014NJ
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Kazdoba-Leach
GivenName
Tatiana
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2013-12-17 00:02:52
AssociatedEntity
Name
Tatiana Kazdoba-Leach
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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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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