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Nitric oxide synthase 1 adaptor protein as a target for treatment of schizophrenia

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TitleInfo
Title
Nitric oxide synthase 1 adaptor protein as a target for treatment of schizophrenia
Name (type = personal)
NamePart (type = family)
Svane
NamePart (type = given)
Kirsten
NamePart (type = date)
1991-
DisplayForm
Kirsten Svane
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Firestein
NamePart (type = given)
Bonnie L
DisplayForm
Bonnie L Firestein
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Silverstein
NamePart (type = given)
Steven M
DisplayForm
Steven M Silverstein
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Moore
NamePart (type = given)
Jennifer
DisplayForm
Jennifer Moore
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Schizophrenia (SCZ) is a severe mental illness that affects 1% of the U.S. population. Antipsychotic medications are ineffective for many patients with SCZ, and N-methyl D-aspartate receptor (NMDAR) agonists may be potential treatments. Nitric oxide synthase 1 adaptor protein (NOS1AP) is overexpressed in the dorsolateral prefrontal cortex of patients with SCZ. NOS1AP negatively regulates NMDAR signaling and reduces dendrite branching in vitro, reproducing the abnormalities in dendrite branching observed in patients with SCZ. Here, we investigate 1) the effects of antipsychotics and NMDAR agonists on function and expression of NOS1AP, dopamine receptor D2 (D2), and disrupted in SCZ 1 (DISC1), and 2) the potential of NOS1AP as a biomarker for SCZ using human buccal cells to screen for NOS1AP expression. First, we treated cortical neurons with antipsychotics or NMDAR agonists (GLYX-13 and D-serine) for 24 hours and used Western blot analysis to determine the effects of these drugs on NOS1AP expression. Using Sholl analysis, we analyzed effects on dendrite branching in cortical rat neurons overexpressing NOS1AP. Additionally, we administered haloperidol or D-serine to male and female Sprague Dawley rats via intraperitoneal injection for 12 days. We used Western blot analysis to determine the effects of treatment on cortical expression of NOS1AP, D2 receptor, and DISC1. Antipsychotics did not affect NOS1AP expression or dendrite branching in vitro, while GLYX-13 and D-serine reduced expression and corrected NOS1AP-mediated reductions in dendrite branching. Haloperidol significantly reduced D2 receptor expression in male, but not female, rats. Importantly, D-serine reduced NOS1AP expression in male, but not female, rats and had no effect on D2 receptor expression. D-serine also showed sex-specific effects on expression of disrupted in SCZ 1 (DISC1). To investigate the potential of NOS1AP as a biomarker for SCZ, we first collected buccal swabs from healthy control subjects. Using Western blot analysis, we confirmed that NOS1AP is consistently expressed in buccal cells, which had never before been investigated. We then assessed buccal cell NOS1AP expression in patients with SCZ and genotyped patients and healthy control subjects for single nucleotide polymorphisms (SNPs) in NOS1AP. Our data indicate that NOS1AP expression may be elevated in patients with SCZ who show rare disease-associated alleles in NOS1AP. Taken together, our data show for the first time that 1) D-serine influences the function and expression of NOS1AP, D2 receptor, and DISC1 in a sex-specific manner, and 2) buccal cell NOS1AP may be a biomarker for SCZ.
Subject (authority = RUETD)
Topic
Neuroscience
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8550
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (vi, 49 p. : ill.)
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Nitric oxide
Subject (authority = ETD-LCSH)
Topic
Schizophrenia--Treatment
Note (type = statement of responsibility)
by Kirsten Svane
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T30Z76G5
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Svane
GivenName
Kirsten
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-12-06 17:24:27
AssociatedEntity
Name
Kirsten Svane
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2020-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ETD
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windows xp
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2017-11-27T14:52:40
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2017-11-27T14:52:40
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