Vitamin D Prevents Cognitive Decline and Enhances Hippocampal Synaptic Function in Aging Rats


Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.

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Published in Proceedings of the National Academy of Sciences of the United States of America, v. 111, no. 41, p. E4359-E4366.

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This research was jointly funded by the National Institute on Aging (NIA) and the McKnight Brain Research Foundation Grant AG034605 (to P.W.L.); other grants from the NIA include AG004542 (to P.W.L.), AG033649 (to O.T.), AG037868 (to E.M.B.), AG010836 (to N.M.P.), and T32 AG000242 (to Greg Gerhardt).