Abstract
BackgroundIncreasing 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.MethodsMale 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.ResultsOur 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.ConclusionsOur 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.
Highlights
Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline
Plasma levels of vitamin D To determine age-related vitamin D changes we measured circulating levels of its active form, vitamin D, 1, α25-dihydroxyvitamin D3, and found significantly lower levels in the aged rats when compared to the young animals (Figure 3); but the deficiency seen in the aged rats that received the supplementation was significantly less in comparison to the aged CON animals
The aged vitamin D group performed significantly better when compared to the aged CON rats, they still demonstrated impairment in comparison to the young animal groups
Summary
Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. Evidence shows that the receptors for vitamin D in the central nervous system (CNS) are widely distributed and that the enzyme responsible for the synthesis of the active form of vitamin D is ubiquitous in the brain [3,4,5]. Based on this information, it is highly likely that vitamin D plays a role in neurological functioning. Other studies suggest the possibility that vitamin D may be neuroprotective because it plays an important role in the expression of neurotrophic factors, neurogenesis, calcium homeostasis, and detoxification [17,18,19,20]
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