Prominent hippocampal CA3 gene expression profile in neurocognitive aging

Rebecca P. Haberman; Carlo Colantuoni; Amy M. Stocker; Alexandra C. Schmidt; Jan T. Pedersen; Michela Gallagher

doi:10.1016/j.neurobiolaging.2009.10.005

Prominent hippocampal CA3 gene expression profile in neurocognitive aging

Rebecca P. Haberman, Carlo Colantuoni, Amy M. Stocker, Alexandra C. Schmidt, Jan T. Pedersen, Michela Gallagher

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Research in aging laboratory animals has characterized physiological and cellular alterations in medial temporal lobe structures, particularly the hippocampus, that are central to age-related memory deficits. The current study compares molecular alterations across hippocampal subregions in a rat model that closely mirrors individual differences in neurocognitive features of aging humans, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between genes and pathways related to chronological age and those associated with impaired or preserved cognitive outcomes in healthy aged Long-Evans rats. The CA3 profile exhibited the most prominent gene expression differences related to cognitive status and of the three subregions, best distinguished preserved from impaired function among the aged animals. Within this profile differential expression of synaptic plasticity and neurodegenerative disease-related genes suggests recruitment of adaptive mechanisms to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.

Original language	English (US)
Pages (from-to)	1678-1692
Number of pages	15
Journal	Neurobiology of aging
Volume	32
Issue number	9
DOIs	https://doi.org/10.1016/j.neurobiolaging.2009.10.005
State	Published - Sep 2011

Keywords

Hippocampus
Preserved cognition
Spatial memory
Synaptic plasticity

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2009.10.005

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title = "Prominent hippocampal CA3 gene expression profile in neurocognitive aging",

abstract = "Research in aging laboratory animals has characterized physiological and cellular alterations in medial temporal lobe structures, particularly the hippocampus, that are central to age-related memory deficits. The current study compares molecular alterations across hippocampal subregions in a rat model that closely mirrors individual differences in neurocognitive features of aging humans, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between genes and pathways related to chronological age and those associated with impaired or preserved cognitive outcomes in healthy aged Long-Evans rats. The CA3 profile exhibited the most prominent gene expression differences related to cognitive status and of the three subregions, best distinguished preserved from impaired function among the aged animals. Within this profile differential expression of synaptic plasticity and neurodegenerative disease-related genes suggests recruitment of adaptive mechanisms to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.",

keywords = "Hippocampus, Preserved cognition, Spatial memory, Synaptic plasticity",

author = "Haberman, {Rebecca P.} and Carlo Colantuoni and Stocker, {Amy M.} and Schmidt, {Alexandra C.} and Pedersen, {Jan T.} and Michela Gallagher",

note = "Funding Information: The authors would like to thank the JHMI Microarray core facility for array processing, Weidong Hu, Ming Teng Koh and Joanne Lee for technical assistance, Giovanni Parmigiani for bioinformatics consultation. The monoclonal antibody Kv4.2 was obtained from the UC Davis/NIH NeuroMab Facility, supported by NIH grant U24NS050606 and maintained by the University of California, Davis. This work was supported by National Institute on Aging/National Institutes of Health Grant P01AG09973 , and a Freedom to Discover Award to MG from the Bristol Myers Squibb Foundation. ",

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AU - Colantuoni, Carlo

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AU - Pedersen, Jan T.

AU - Gallagher, Michela

N1 - Funding Information: The authors would like to thank the JHMI Microarray core facility for array processing, Weidong Hu, Ming Teng Koh and Joanne Lee for technical assistance, Giovanni Parmigiani for bioinformatics consultation. The monoclonal antibody Kv4.2 was obtained from the UC Davis/NIH NeuroMab Facility, supported by NIH grant U24NS050606 and maintained by the University of California, Davis. This work was supported by National Institute on Aging/National Institutes of Health Grant P01AG09973 , and a Freedom to Discover Award to MG from the Bristol Myers Squibb Foundation.

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N2 - Research in aging laboratory animals has characterized physiological and cellular alterations in medial temporal lobe structures, particularly the hippocampus, that are central to age-related memory deficits. The current study compares molecular alterations across hippocampal subregions in a rat model that closely mirrors individual differences in neurocognitive features of aging humans, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between genes and pathways related to chronological age and those associated with impaired or preserved cognitive outcomes in healthy aged Long-Evans rats. The CA3 profile exhibited the most prominent gene expression differences related to cognitive status and of the three subregions, best distinguished preserved from impaired function among the aged animals. Within this profile differential expression of synaptic plasticity and neurodegenerative disease-related genes suggests recruitment of adaptive mechanisms to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.

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Prominent hippocampal CA3 gene expression profile in neurocognitive aging

Abstract

Keywords

ASJC Scopus subject areas

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