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Open Access Highly Accessed Research

Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden

Teresita L Briones1* and Hala Darwish2

Author Affiliations

1 Department of Adult Health, Wayne State University, 5557 Cass Ave., Cohn Bldg, Rm 344, Detroit, MI 48202, USA

2 Hariri School of Nursing, American University of Beirut, Beirut, Lebanon

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Journal of Neuroinflammation 2012, 9:244  doi:10.1186/1742-2094-9-244

Published: 25 October 2012

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg for 21 days. Control animals received equal volume of normal saline. Behavioral testing in water maze and spontaneous object recognition tasks started on day 14. Levels of interleukin (IL)-1β and IL-10 were quantified to assess inflammatory state. Also, beta amyloid (Aβ) clearance and Aβ load were measured.

Results

Our results show that: (1) aged rats demonstrated significant learning and memory impairment overall compared to younger animals. However, the age-related decline in learning and memory was ameliorated by the supplementation of vitamin D. No vitamin D effect on learning and memory was seen in the young animals; 2) the pro-inflammatory cytokine IL-1β is significantly increased while the anti-inflammatory cytokine IL-10 is significantly decreased in the aged rats compared to the young animals; but this age-related change in inflammatory state was mitigated by vitamin D supplementation. No effects of vitamin D were seen on the IL-1β and IL-10 expression in the young rats; (3) vitamin D increased Aβ clearance and decreased amyloid burden in the aged rats while no significant difference was seen between the young animal groups.

Conclusions

Our data suggest that vitamin D supplementation modulated age-related increase in pro-inflammatory state and amyloid burden. It is possible that these effects of vitamin D mediated the decrease memory impairment seen in the aged rats making it a useful therapeutic option to alleviate the effects of aging on cognitive function.

Keywords:
Learning and memory; Object recognition test; IL-1β; IL-10; Aging; Cognitive aging