The aging hippocampus: A multi-level analysis in the rat

• Published in: Neuroscience Vol. 139; no. 4; pp. 1173 - 1185
• Main Authors: Driscoll, I., Howard, S.R., Stone, J.C., Monfils, M.H., Tomanek, B., Brooks, W.M., Sutherland, R.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: Aging - physiology; Animals; Behavior, Animal - physiology; Biological and medical sciences; Bromodeoxyuridine - pharmacokinetics; Discrimination (Psychology) - physiology; FBNF1; Female; Fundamental and applied biological sciences. Psychology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Immunohistochemistry - methods; Ki-67 Antigen - metabolism; Magnetic Resonance Imaging - methods; Maze Learning - physiology; Microtubule-Associated Proteins - metabolism; Morris water task; MRI; MRS; Multivariate Analysis; neurogenesis; Neuropeptides - metabolism; Phosphopyruvate Hydratase - metabolism; Positron-Emission Tomography - methods; Rats; Rats, Inbred F344; Spatial Behavior - physiology; transverse patterning; Vertebrates: nervous system and sense organs; Morris water task; transverse patterning; IBD/NRC; PBS; DG; FBNF1; MRI; 1H MRS; NIA; EM; TPD; Cho; MWT; ROI; MRS; NAA; V dis; ANOVA; Cre; neurogenesis; DCX; ICV; BrdU; CA; Senescence; Rat; Rodentia; Central nervous system; Nuclear magnetic resonance imaging; Neurogenesis; Encephalon; Vertebrata; Mammalia; Animal; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.01.040

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 344×Brown 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.