Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

Caitlin S. Latimer, Lawrence D. Brewer, James L. Searcy, Kuey Chu Chen, Jelena Popović, Susan D. Kraner, Olivier Thibault, Eric M. Blalock, Philip W. Landfield, Nada M. Porter

Research output: Contribution to journalArticlepeer-review

162 Citations (SciVal)


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 deficiencymay 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.

Original languageEnglish
Pages (from-to)E4359-E4366
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 14 2014

Bibliographical note

Publisher Copyright:
© 2014, National Academy of Sciences. All rights reserved.


  • 25-hydroxyvitamin D
  • Cholecalciferol
  • Vitamin D status

ASJC Scopus subject areas

  • General


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