CALORIC RESTRICTION INCREASES BRAIN-DERIVED NEUROTROPHIC FACTOR LEVELS IN AREA CA1 OF THE RAT HIPPOCAMPUS





I. G. Newton*, M. E. Forbes, D. R. Riddle, J. K. Brunso-Bechtold

Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157



Caloric restriction (CR) extends lifespan and retards age-related diseases and degenerative processes in the body and the brain. Moreover, CR prevents the decline in behavioral measures of hippocampus-dependent learning and memory after middle age in Fischer 344 x Brown-Norway (F344xBN) rats (Markowska et al, 2002). CR may protect learning and memory by modulating neurotrophic activity. Brain-derived neurotrophic factor (BDNF) is a candidate to mediate age- and CR-dependent effects on learning and memory, since it influences potential substrates of hippocampal function, including synapse density, synaptic efficacy and long-term potentiation. The literature is inconclusive regarding the effects of age or CR on BDNF levels in the hippocampus, in part because previous measurements have lacked the resolution to detect changes within hippocampal subfields, which exhibit very different levels of BDNF immunoreactivity. One might speculate that the age-related decline in learning and memory reflects a decrease in BDNF levels and that CR preserves hippocampal function by increasing BDNF levels as compared to age-matched AL controls. We measured BDNF in the hippocampal subregions dentate gyrus (DG), area CA3 and area CA1 of male F344xBN rats at ages 10, 18 and 29 months using an electrochemiluminescence immunoassay (ECLIA) (N=5 rats/condition). Surprisingly, BDNF levels were found to increase with age in DG of both AL and CR rats. No age-related change in BDNF levels was detected in CA3 or CA1. In area CA1 of old rats, BDNF levels were greater in CR versus AL rats. CR rats exhibited a trend of higher BDNF levels in all regions and at all ages as compared to AL rats. In conclusion, the observed increase in DG BDNF levels across ages, independent of diet, may constitute a compensatory response to age-related degenerative processes in this area. Furthermore, CR may preserve hippocampal function after middle age in the F344xBN rat by increasing CA1 BDNF levels in old age. NIA AG11370& AG019886




Key words: Caloric Restriction, Brain-derived neurotrophic factor, Aging, Hippocampus, Fischer 344 x Brown Norway rat







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