title: Hippocampal subregions exhibit both distinct and shared transcriptomic responses to aging and nonneurodegenerative cognitive decline.
abstract: Impairment of hippocampal-dependent spatial learning and memory with aging affects a large segment of the aged population. Hippocampal subregions (CA1, CA3, and DG) have been previously reported to express both common and specific morphological, functional, and gene/protein alterations with aging and cognitive decline. To comprehensively assess gene expression with aging and cognitive decline, transcriptomic analysis of CA1, CA3, and DG was conducted using Adult (12M) and Aged (26M) F344xBN rats behaviorally characterized by Morris water maze performance. Each subregion demonstrated a specific pattern of responses with aging and with cognitive performance. The CA1 and CA3 demonstrating the greatest degree of shared gene expression changes. Analysis of the pathways, processes, and regulators of these transcriptomic changes also exhibit a similar pattern of commonalities and differences across subregions. Gene expression changes between Aged cognitively Intact and Aged cognitively Impaired rats often showed an inversion of the changes between Adult and Aged rats. This failure to adapt rather than an exacerbation of the aging phenotype questions a conventional view that cognitive decline is exaggerated aging. These results are a resource for investigators studying cognitive decline and also demonstrate the need to individually examine hippocampal subregions in molecular analyses of aging and cognitive decline.
authors.affiliation: Department of Physiology and Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center.
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Masser
authors.affiliation: Genome Sciences Facility, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Bixler
authors.affiliation: Genome Sciences Facility, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brucklacher
authors.affiliation: Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Arthritis & Clinical Immunology Program, Oklahoma Medicine Research Foundation.
authors.forename: Cory B
authors.initials: CB
authors.lastname: Giles
authors.affiliation: Arthritis & Clinical Immunology Program, Oklahoma Medicine Research Foundation.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wren
authors.affiliation: Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center.
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.affiliation: Department of Physiology and Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center. wfreeman@ouhsc.edu.
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
mesh_terms: D000375:Aging / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D018891:Dentate Gyrus / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D059467:Transcriptome
keywords: Aging; Cognitive impairment.; Gene expression; Hippocampus