title: Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats.
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.
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Latimer
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Brewer
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: James L
authors.initials: JL
authors.lastname: Searcy
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Kuey-Chu
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Jelena
authors.initials: J
authors.lastname: Popović
authors.affiliation: Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, KY 40536.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Kraner
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Thibault
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Blalock
authors.affiliation: Department of Pharmacology and Nutritional Sciences and.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Landfield
authors.affiliation: Department of Pharmacology and Nutritional Sciences and nadap@uky.edu.
authors.forename: Nada M
authors.initials: NM
authors.lastname: Porter
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control*; D004032:Diet; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011916:Rats, Inbred F344; D020218:Response Elements / Q000235:genetics; D012984:Software; D009435:Synaptic Transmission / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014807:Vitamin D
keywords: 25-hydroxyvitamin D; Vitamin D status; cholecalciferol