Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
We have carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze. By using Affymetrix GeneChip microarrays, we found a distinct pattern of age-related change, consisting mostly of gene overexpression in the middle-aged mice, suggesting that the induction of negative regulators in the middle-aged hippocampus could be involved in impairment of learning. Interestingly, we report changes in transcript levels for genes that could affect synaptic plasticity. Those changes could be involved in the memory deficits we observed in the 15-month-old mice. In agreement with previous reports, we also found altered expression in genes related to inflammation, protein processing, and oxidative stress.
Verbitsky
Miguel
M
Columbia Genome Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Yonan
Amanda L
AL
Malleret
Gaël
G
Kandel
Eric R
ER
Gilliam
T Conrad
TC
Pavlidis
Paul
P
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004193:Discrimination Learning / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D013028:Space Perception / Q000502:physiology; D013037:Spatial Behavior
D012333:RNA, Messenger