Gabaergic Systems and Age-Related Cognitive Decline

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Material Information

Title:
Gabaergic Systems and Age-Related Cognitive Decline
Physical Description:
1 online resource (164 p.)
Language:
english
Creator:
Banuelos, Cristina
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Medical Sciences, Neuroscience (IDP)
Committee Chair:
BIZON,JENNIFER L
Committee Co-Chair:
SETLOW,BARRY
Committee Members:
FOSTER,THOMAS C
FRAZIER,CHARLES JASON
SMITH,DAVID WILLIAM

Subjects

Subjects / Keywords:
aging -- gaba -- hippocampus -- learning -- memory
Neuroscience (IDP) -- Dissertations, Academic -- UF
Genre:
Medical Sciences thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
With advances in medical science contributing to increased longevity, it is becoming increasingly important to elucidate the neural factors that underlie age-related declines in cognitive functions and to develop strategies that can promote healthy cognitive outcomes across the full lifespan. The hippocampus and the prefrontal cortex are two brain regions implicated in cognitive function and both these regions are highly sensitive to changes in aging. The overarching goal of this dissertation was to investigate how aging alters inhibitory signaling in a rodent model of normal aging, and to determine how such changes impact both hippocampal- and prefrontal cortical- dependent cognition. In Chapter 2 western blotting was used to quantify GABAergic signaling protein expression in hippocampus and confocal stereology was used to quantify phenotypically-specific neuron populations in basal forebrain of young and aged rats that were first behaviorally characterized on a septohippocampal-dependent water maze task. While the expression of most GABAergic signaling proteins in hippocampus did not change with age, expression of glutamic decarboxylase (GAD67) was selectively reduced in aged rats with spatial learning impairment. Moreover, GABAergic projection neuron number in basal forebrain was increased in aged animals with spatial learning impairments. Together, these data support that altered GABAergic signaling in the septohippocampal system contributes to age-related memory decline. In Chapter 3, western blotting was used to assess the expression of GABAergic signaling proteins in the prefrontal cortex of young and aged rats that were first behaviorally characterized on an operant delayed-response test of working memory. Prefrontal cortical expression of the GABA synthesizing enzyme GAD67 was increased and the neuronal GABA transporter, GAT-1, was decreased with age. GABA(B) receptor (GABA(B)R) expression was also reduced in aged prefrontal cortex (PFC). GABA(B)R expression was significantly and inversely associated with working memory such that those aged rats with lower GABA(B)R expression exhibited better delayed response performance. These data suggest that aging is accompanied by increased GABA availability within PFC and that downregulation of GABA(B)R expression may preserve appropriate levels of tonic inhibition required for optimal working memory. Pharmacological studies were conducted which supported this hypothesis as administration of a GABA(B)R antagonist, both systemically and directly into the prefrontal cortex, significantly improved working memory performance in impaired aged rats, restoring cognitive function to a level on par with young. Together, the data presented in this dissertation demonstrate that GABAergic systems are significantly altered in aging and that these alterations play a causal role in age-related cognitive decline. In addition, pharmacologically targeting this system, specifically through GABA(B) receptors, improves working memory performance in aged rats indicating that this system may serve as a therapeutic target for treating cognitive decline in aging.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Cristina Banuelos.
Thesis:
Thesis (Ph.D.)--University of Florida, 2014.
Local:
Adviser: BIZON,JENNIFER L.
Local:
Co-adviser: SETLOW,BARRY.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-11-30

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2014
System ID:
UFE0046176:00001