title: Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden.
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.
authors.affiliation: Department of Adult Health, Wayne State University, 5557 Cass Ave, Cohn Bldg, Rm 344, Detroit, MI 48202, USA. tbriones@wayne.edu
authors.forename: Teresita L
authors.initials: TL
authors.lastname: Briones
authors.forename: Hala
authors.initials: H
authors.lastname: Darwish
mesh_terms: D000375:Aging; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000178:diet therapy*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015260:Neprilysin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D021641:Recognition, Psychology / Q000187:drug effects; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D012333:RNA, Messenger; D014807:Vitamin D; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D015260:Neprilysin