The aging hippocampus: a multi-level analysis in the rat.
In the current experiment we conducted a multi-level analysis of age-related characteristics in the hippocampus of young adult (3 months), middle-aged (12 months), and old (24 months) Fisher 344xBrown Norway hybrid (FBNF1) rats. We examined the relationships between aging, hippocampus, and memory using a combination of behavioral, non-invasive magnetic resonance imaging and spectroscopy, and postmortem neuroanatomical measures in the same rats. Aging was associated with functional deficits on hippocampus-dependent memory tasks, accompanied by structural alterations observed both in vivo (magnetic resonance imaging-hippocampal volume) and postmortem (dentate gyrus neuronal density and neurogenesis). Neuronal metabolic integrity, assessed by levels of N-acetylaspartate with magnetic resonance spectroscopy, was however, preserved. Further, our results suggest that neurogenesis (doublecortin) seems to be related to both performance deficits on hippocampus-dependent tasks and hippocampal volume reduction. The observed pattern of age-related alterations closely resembles that previously reported in humans and suggests FBNF1 rats to be a useful model of normal human aging.
Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Alberta. driscolli@mailnih.gov
I
I
Driscoll
S R
SR
Howard
J C
JC
Stone
M H
MH
Monfils
B
B
Tomanek
W M
WM
Brooks
R J
RJ
Sutherland
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D004192:Discrimination, Psychological / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D018782:Maze Learning / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015999:Multivariate Analysis; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D013037:Spatial Behavior / Q000502:physiology
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine