Hippocampal Subregions Exhibit Both Distinct and Shared Transcriptomic Responses to Aging and Nonneurodegenerative Cognitive Decline

被引:40
作者
Masser, Dustin R. [1 ,2 ]
Bixler, Georgina V. [3 ]
Brucklacher, Robert M. [3 ]
Yan, Han [2 ]
Giles, Cory B. [4 ]
Wren, Jonathan D. [4 ]
Sonntag, William E. [2 ]
Freeman, Willard M. [1 ,2 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Norman, OK 73019 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Norman, OK 73019 USA
[3] Penn State Coll Med, Genome Sci Facil, Hershey, PA USA
[4] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA
来源
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2014年 / 69卷 / 11期
关键词
Gene expression; Hippocampus; Aging; Cognitive impairment; SPATIAL-LEARNING DEFICITS; FACTOR HOMOLOGOUS FACTORS; GATED SODIUM-CHANNELS; AGED RATS; SYNAPTIC PLASTICITY; NEURON NUMBER; MESSENGER-RNA; RETT-SYNDROME; CORDON-BLEU; EXPRESSION;
D O I
10.1093/gerona/glu091
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:1311 / 1324
页数:14
相关论文
共 65 条
[21]   Isolation of a novel human gene, ARHGAP9, encoding a Rho-GTPase activating protein [J].
Furukawa, Y ;
Kawasoe, T ;
Daigo, Y ;
Nishiwaki, T ;
Ishiguro, H ;
Takahashi, M ;
Kitayama, J ;
Nakamura, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 284 (03) :643-647
[22]   Fibroblast growth factor homologous factors control neuronal excitability through modulation of voltage-gated sodium channels [J].
Goldfarb, Mitchell ;
Schoorlemmer, Jon ;
Williams, Anthony ;
Diwakar, Shyam ;
Wang, Cling ;
Huan, Xiao ;
Giza, Joanna ;
Tchetchik, Dafna ;
Kelley, Kevin ;
Vega, Ana ;
Matthews, Gary ;
Rossi, Paola ;
Ornitz, David M. ;
D'Angelo, Egidio .
NEURON, 2007, 55 (03) :449-463
[23]   THE AGED MOUSE AS A MODEL OF COGNITIVE DECLINE WITH SPECIAL EMPHASIS ON STUDIES IN NMRI MICE [J].
GOWER, AJ ;
LAMBERTY, Y .
BEHAVIOURAL BRAIN RESEARCH, 1993, 57 (02) :163-173
[24]   Quantitative Transcriptional Neuroanatomy of the Rat Hippocampus: Evidence for Wide-Ranging, Pathway-Specific Heterogeneity Among Three Principal Cell Layers [J].
Greene, James G. ;
Borges, Karin ;
Dingledine, Raymond .
HIPPOCAMPUS, 2009, 19 (03) :253-264
[25]   The Actin Nucleator Cobl Is Crucial for Purkinje Cell Development and Works in Close Conjunction with the F-Actin Binding Protein Abp1 [J].
Haag, Natja ;
Schwintzer, Lukas ;
Ahuja, Rashmi ;
Koch, Nicole ;
Grimm, Julia ;
Heuer, Heike ;
Qualmann, Britta ;
Kessels, Michael M. .
JOURNAL OF NEUROSCIENCE, 2012, 32 (49) :17842-17856
[26]   Prominent hippocampal CA3 gene expression profile in neurocognitive aging [J].
Haberman, Rebecca P. ;
Colantuoni, Carlo ;
Stocker, Amy M. ;
Schmidt, Alexandra C. ;
Pedersen, Jan T. ;
Gallagher, Michela .
NEUROBIOLOGY OF AGING, 2011, 32 (09) :1678-1692
[27]   Insights into the ageing mind: A view from cognitive neuroscience [J].
Hedden, T ;
Gabrieli, JDE .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (02) :87-U12
[28]   The aging brain: morphomolecular senescence of cortical circuits [J].
Hof, PR ;
Morrison, JH .
TRENDS IN NEUROSCIENCES, 2004, 27 (10) :607-613
[29]   Hippocampal and Cognitive Aging across the Lifespan: A Bioenergetic Shift Precedes and Increased Cholesterol Trafficking Parallels Memory Impairment [J].
Kadish, Inga ;
Thibault, Olivier ;
Blalock, Eric M. ;
Chen, Kuey-C. ;
Gant, John C. ;
Porter, Nada M. ;
Landfield, Philip W. .
JOURNAL OF NEUROSCIENCE, 2009, 29 (06) :1805-1816
[30]   Expression of Novel Alzheimer's Disease Risk Genes in Control and Alzheimer's Disease Brains [J].
Karch, Celeste M. ;
Jeng, Amanda T. ;
Nowotny, Petra ;
Cady, Janet ;
Cruchaga, Carlos ;
Goate, Alison M. .
PLOS ONE, 2012, 7 (11)