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

Significance Higher blood levels of vitamin D are associated with better health outcomes. Vitamin D deficiency, however, is common among the elderly. Despite targets in the brain, little is known about how vitamin D affects cognitive function. In aging rodents, we modeled human serum vitamin D level...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-10, Vol.111 (41), p.E4359-E4366
Main Authors: Latimer, Caitlin S, Brewer, Lawrence D, Searcy, James L, Chen, Kuey-Chu, Popović, Jelena, Kraner, Susan D, Thibault, Olivier, Blalock, Eric M, Landfield, Philip W, Porter, Nada M
Format: Article
Language:English
Subjects:
Aging - drug effects
Aging - pathology
Animal cognition
Animals
Biological Sciences
Brain
Cognition Disorders - drug therapy
Cognition Disorders - physiopathology
Cognition Disorders - prevention & control
Diet
Gene expression
Hippocampus - drug effects
Hippocampus - pathology
Hippocampus - physiopathology
Hormones
Humans
Male
Maze Learning - drug effects
Models, Neurological
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
PNAS Plus
Rats, Inbred F344
Response Elements - genetics
Rodents
Software
Synaptic Transmission - drug effects
Up-Regulation - drug effects
Vitamin D
Vitamin D - blood
Vitamin D - pharmacology
Vitamin D - therapeutic use
Vitamin deficiency
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Summary:Significance Higher blood levels of vitamin D are associated with better health outcomes. Vitamin D deficiency, however, is common among the elderly. Despite targets in the brain, little is known about how vitamin D affects cognitive function. In aging rodents, we modeled human serum vitamin D levels ranging from deficient to sufficient and tested whether increasing dietary vitamin D could maintain or improve cognitive function. Treatment was initiated at middle age, when markers of aging emerge, and maintained for ∼6 mo. Compared with low- or normal-dietary vitamin D groups, only aging rats on higher vitamin D could perform a complex memory task and had blood levels considered in the optimal range. These results suggest that vitamin D may improve the likelihood of healthy cognitive aging. 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1404477111