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

Authors

Caitlin S. Latimer, University of Kentucky
Lawrence D. Brewer, University of KentuckyFollow
James L. Searcy, University of Kentucky
Kuey-Chu Chen, University of KentuckyFollow
Jelena Popovic, University of KentuckyFollow
Susan D. Kraner, University of KentuckyFollow
Olivier Thibault, University of KentuckyFollow
Eric M. Blalock, University of KentuckyFollow
Philip W. Landfield, University of KentuckyFollow
Nada M. Porter, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

10-14-2014

Notes/Citation Information

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

Digital Object Identifier (DOI)

http://dx.doi.org/10.1073/pnas.1404477111

Funding Information

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).

Repository Citation

Latimer, Caitlin S.; Brewer, Lawrence D.; Searcy, James L.; Chen, Kuey-Chu; Popovic, Jelena; Kraner, Susan D.; Thibault, Olivier; Blalock, Eric M.; Landfield, Philip W.; and Porter, Nada M., "Vitamin D Prevents Cognitive Decline and Enhances Hippocampal Synaptic Function in Aging Rats" (2014). Pharmacology and Nutritional Sciences Faculty Publications. 28.
https://uknowledge.uky.edu/pharmacol_facpub/28