Subregion Specific Changes In Immediate-Early Genes in the Aged Hippocampus

Persistent Link:
http://hdl.handle.net/10150/194312
Title:
Subregion Specific Changes In Immediate-Early Genes in the Aged Hippocampus
Author:
Penner, Marsha Rae
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The normal aging process is accompanied by changes in cognitive function. One of the brain regions known to be an early target of the aging process is the hippocampus, a medial temporal lobe structure that is critically involved in spatial learning and memory function. The formation and maintenance of memory relies on rapid and sustainable synaptic modification, which requires new gene expression. Immediate-early genes are the first genes to be induced following relevant stimuli, and include genes that encode transcription factors, such as c-fos and zif268, and effector proteins that directly influence cellular function, such as Arc (activity-regulated cytoskeletal gene) and Homer1A. Blocking the expression of any one of these genes interferes with memory function, and thus, each of these genes is thought to have a memory enhancing effect. The hypothesis tested here was that aged animals would show a reduction in the expression of memory-promoting immediate-early genes within the hippocampus, and moreover, that these changes in expression would be subregion specific, based on the finding that the dentate gyrus is most vulnerable to the aging process.Potential age-related changes in immediate-early gene expression within the hippocampus was determined under basal conditions and after induction by a simple behavioral task. Of the genes under investigation, only c-fos did not show age-related changes under basal conditions, or following behavioral induction. The remaining genes, Arc, zif268 and Homer1A, each showed subregion specific patterns of change within the hippocampus under basal conditions or following induction (or both). The coordinate expression of immediate-early genes within the hippocampus was also investigated by assessing the extent to which Arc was expressed within the same neurons as c-fos, zif268 or H1a. The coordinate transcription of these genes was not significantly altered in the aged hippocampus, even though changes in the size of Arc and zif268 neural ensembles occurs within the aged denate gyrus.Taken together, these data indicate that age-related reductions in the basal and induced levels of immediate-early genes occur within the hippocampus, and that these changes are subregion specific.
Type:
text; Electronic Dissertation
Keywords:
Aging; Gene Expression; Hippocampus
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Neuroscience; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Barnes, Carol A
Committee Chair:
Barnes, Carol A

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleSubregion Specific Changes In Immediate-Early Genes in the Aged Hippocampusen_US
dc.creatorPenner, Marsha Raeen_US
dc.contributor.authorPenner, Marsha Raeen_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe normal aging process is accompanied by changes in cognitive function. One of the brain regions known to be an early target of the aging process is the hippocampus, a medial temporal lobe structure that is critically involved in spatial learning and memory function. The formation and maintenance of memory relies on rapid and sustainable synaptic modification, which requires new gene expression. Immediate-early genes are the first genes to be induced following relevant stimuli, and include genes that encode transcription factors, such as c-fos and zif268, and effector proteins that directly influence cellular function, such as Arc (activity-regulated cytoskeletal gene) and Homer1A. Blocking the expression of any one of these genes interferes with memory function, and thus, each of these genes is thought to have a memory enhancing effect. The hypothesis tested here was that aged animals would show a reduction in the expression of memory-promoting immediate-early genes within the hippocampus, and moreover, that these changes in expression would be subregion specific, based on the finding that the dentate gyrus is most vulnerable to the aging process.Potential age-related changes in immediate-early gene expression within the hippocampus was determined under basal conditions and after induction by a simple behavioral task. Of the genes under investigation, only c-fos did not show age-related changes under basal conditions, or following behavioral induction. The remaining genes, Arc, zif268 and Homer1A, each showed subregion specific patterns of change within the hippocampus under basal conditions or following induction (or both). The coordinate expression of immediate-early genes within the hippocampus was also investigated by assessing the extent to which Arc was expressed within the same neurons as c-fos, zif268 or H1a. The coordinate transcription of these genes was not significantly altered in the aged hippocampus, even though changes in the size of Arc and zif268 neural ensembles occurs within the aged denate gyrus.Taken together, these data indicate that age-related reductions in the basal and induced levels of immediate-early genes occur within the hippocampus, and that these changes are subregion specific.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectAgingen_US
dc.subjectGene Expressionen_US
dc.subjectHippocampusen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNeuroscienceen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBarnes, Carol Aen_US
dc.contributor.chairBarnes, Carol Aen_US
dc.contributor.committeememberRyan, Leeen_US
dc.contributor.committeememberWenk, Garyen_US
dc.contributor.committeememberGordon, Hermanen_US
dc.contributor.committeememberBarnes, Carolen_US
dc.identifier.proquest2618en_US
dc.identifier.oclc659748540en_US
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