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The role of serotonergic dysfunction in the etiology of affective disorder in a Huntington’s disease translational mouse model
Descriptive
TitleInfo
Title
The role of serotonergic dysfunction in the etiology of affective disorder in a Huntington’s disease translational mouse model
Name
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Alselehdar
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Samar K.
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1989-
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Samar K. Alselehdar
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author
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James
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James Tepper
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Advisory Committee
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chair
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Abercrombie
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Elizabeth
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Elizabeth Abercrombie
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Advisory Committee
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internal member
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(type = family)
Mena-Segovia
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(type = given)
Juan
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Juan Mena-Segovia
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Advisory Committee
Role
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internal member
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Shiflett
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(type = given)
Michael
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Michael Shiflett
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Advisory Committee
Role
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internal member
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(type = family)
Zaborszky
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Laszlo
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Laszlo Zaborszky
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Advisory Committee
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internal member
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Hensler
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Julie
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Julie Hensler
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Advisory Committee
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outside member
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Rutgers University
Role
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degree grantor
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Graduate School - Newark
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Text
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theses
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ETD doctoral
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2017
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2017-10
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2017
Place
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xx
Language
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eng
Abstract
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Huntington’s disease (HD) is an autosomal dominant, progressive neurodegenerative disorder that manifests with a triad of psychiatric, cognitive, and motor symptoms. The pathophysiology of the psychiatric symptoms is not well understood but is frequently associated with serotonergic dysfunction in limbic-related circuits in the brain. However, it remains unknown how the serotonergic system is impaired in HD. The primary aim of this thesis is to assess the use of a translational mouse model of HD to better understand the contribution of serotonergic dysfunction in the etiology of affective disorders in the disease, and to assess the use of novel therapeutics for the amelioration of symptoms. I conducted tests to quantify the incidence of affective disorder in mice and observed that the BACHD mouse model displays anxiety-like and depressive-like behaviors, which are the two most common psychiatric symptoms in HD patients. Importantly, I found evidence that the psychiatric symptoms in the BACHD mice develop prior to the onset of motor deficits, similar to HD patients. The similar behavioral phenotype of this mouse model enabled further investigation into the role of serotonergic neurotransmission in HD. With the use of in vivo microdialysis, I quantified serotonergic efflux, which is a product of serotonin release, reuptake, metabolism and receptor binding. Serotonin efflux was reduced in the ventral hippocampus but not the dorsal striatum, suggesting that serotonin efflux is only reduced in the limbic ventral hippocampus and that monoaminergic activity (including dopamine) in the dorsal striatum remains intact. With additional tests, I determined that activation of the 5-HT1A receptor using an agonist has an anxiolytic and potential antidepressant effect in the BACHD mouse model. Acute administration of the selective serotonin reuptake inhibitor ameliorated depressive symptoms in the BACHD mice. The dual antidepressant and anxiolytic effect of activation of the 5-HT1A receptor is suggestive that serotonergic dysfunction in the BACHD mice is a result of impaired communication in postsynaptic targets of the serotonergic system.
Subject
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Topic
Neuroscience
Subject
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Topic
Huntington's disease
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier
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rucore10002600001
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ETD_8359
Identifier
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doi:10.7282/T38P63M2
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xv, 131 p. : ill.)
Note
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Ph.D.
Note
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Includes bibliographical references
Note
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by Samar K. Alselehdar
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NjNbRU
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Alselehdar
GivenName
Samar
MiddleName
K.
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Permission or license
DateTime
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2017-09-18 20:43:13
AssociatedEntity
Name
Samar Alselehdar
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Affiliation
Rutgers University. Graduate School - Newark
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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