Prominent hippocampal CA3 gene expression profile in neurocognitive aging.
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.
Haberman
Rebecca P
RP
Department of Psychological and Brain Science, The Johns Hopkins University, 3400 N Charles Street, 104 Ames Hall, Baltimore, MD 21218, United States. rahabs@jhu.edu
Colantuoni
Carlo
C
Stocker
Amy M
AM
Schmidt
Alexandra C
AC
Pedersen
Jan T
JT
Gallagher
Michela
M
D000222:Adaptation, Physiological / Q000235:genetics; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D056547:CA1 Region, Hippocampal / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics; D058245:Cognitive Reserve / Q000502:physiology; D018891:Dentate Gyrus / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans
D009419:Nerve Tissue Proteins