Staff View
Modeling the circadian regulation of HPA axis activity

Descriptive

TitleInfo
Title
Modeling the circadian regulation of HPA axis activity
Name (type = personal)
NamePart (type = family)
Rao
NamePart (type = given)
Rohit T.
NamePart (type = date)
1990-
DisplayForm
ROHIT RAO
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Androulakis
NamePart (type = given)
Ioannis P
DisplayForm
Ioannis P Androulakis
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Ramachandran
NamePart (type = given)
Rohit
DisplayForm
Rohit Ramachandran
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Roth
NamePart (type = given)
Charles
DisplayForm
Charles Roth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Jusko
NamePart (type = given)
William J
DisplayForm
William J Jusko
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
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)
2018-10
CopyrightDate (encoding = w3cdtf)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The hypothalamic-pituitary-adrenal (HPA) axis constitutes the primary physiological stress response mechanism, with cortisol (corticosterone in rodents) being the major effector molecule of the HPA axis, mediating an array of metabolic and immune-modulatory functions. The circadian dynamics of the mediators of HPA axis are considered to significantly modulate their functional characteristics and demonstrate remarkable plasticity. This is observed in pathological conditions where circadian disruption is often associated with disease etiology, as in the case of chronic inflammatory conditions such as rheumatoid arthritis, as well as in physiological conditions, where the presence of significant sex differences in numerous aspects of the HPA axis, including both basal circadian activity as well as in its response to physiological stressors is well established. It is widely suggested that the mechanisms that dictate the rhythmic properties of the HPA network might also contribute to its functioning in both physiological and pathological conditions. For example, the sex differences in the circadian dynamics of the HPA axis are thought to contribute to the observed sex disparity in the development of a variety of autoimmune and infectious diseases. Moreover, an understanding of these underlying mechanisms is critical to development of pharmacological approaches that can appropriately treat HPA axis disorders. Mathematical modeling provides a promising approach to study physiological feedback systems such as the HPA axis, and enables the evaluation of the feasibility of hypotheses, by providing a phenomenological framework for explaining empirical observations as well as making testable predictions. In this work we develop semi-mechanistic mathematical models of the HPA axis to understand the critical regulatory mechanisms that contribute to its functioning in health and disease. In the first aim we develop a mathematical model for the progression of collagen-induced arthritis that evaluates the effect of chronic elevation on the proinflammatory cytokines on the circadian dynamics of corticosterone and important markers of disease activity such as paw edema, thus emphasizing the importance of accounting for circadian rhythms in models of chronic inflammation. Subsequently, we study how differences in the regulatory features of the HPA network might lead to basal variability, with a focus on sex-specific and individual differences in its activity. In doing so, we predict that the host can employ diverse regulatory mechanisms to maintain glucocorticoid circadian rhythms within strict physiological bounds, ultimately resulting in the existence of trade-offs between multiple functional characteristics of the HPA axis. Furthermore, we characterize specific chronic stress-induced allostatic adaptations in the regulatory dynamics of the HPA axis. Finally, through mathematical modeling, we determine how an understanding of the circadian dynamics of the HPA axis could be leveraged for the design of chronotherapeutic dosing regimens to minimize the incidence of adverse effects associated with chronic glucocorticoid therapy.
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
Subject (authority = ETD-LCSH)
Topic
Glucocorticoids
Subject (authority = ETD-LCSH)
Topic
Hypothalamic-pituitary-adrenal axis
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9075
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (160 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Rohit T. Rao
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/t3-5btj-0d28
Genre (authority = ExL-Esploro)
ETD doctoral
Back to the top

Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Rao
GivenName
Rohit T.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-06-18 12:50:23
AssociatedEntity
Name
ROHIT RAO
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top

Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
CreatingApplication
Version
1.4
ApplicationName
Mac OS X 10.13.4 Quartz PDFContext
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2018-06-21T13:28:10
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2018-06-21T13:28:10
Back to the top
Version 8.5.5
Rutgers University Libraries - Copyright ©2024