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Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

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

Authors: Teresita L Briones, Hala Darwish

Published in: Journal of Neuroinflammation | Issue 1/2012

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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.
Literature
1.
go back to reference Coudray C, O'Connor JM, Maiani G, Cashman KD, Simpson EE, Secker DL, Ferry M, Roussel AM: Introduction to the ZENITH study and summary of baseline results. Eur J Clin Nutr 2005,59(Suppl 2):S5-S7.CrossRefPubMed Coudray C, O'Connor JM, Maiani G, Cashman KD, Simpson EE, Secker DL, Ferry M, Roussel AM: Introduction to the ZENITH study and summary of baseline results. Eur J Clin Nutr 2005,59(Suppl 2):S5-S7.CrossRefPubMed
2.
go back to reference Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA: Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2002, 76:187–192.PubMed Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA: Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2002, 76:187–192.PubMed
3.
go back to reference Kalueff AV, Tuohimaa P: Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care 2007, 10:12–19.CrossRefPubMed Kalueff AV, Tuohimaa P: Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care 2007, 10:12–19.CrossRefPubMed
4.
go back to reference Buell JS, Dawson-Hugues B: Vitamin D and neurocognitive dysfunction: preventing 'D'ecline? Mol Aspects Med 2008, 29:415–422.CrossRefPubMed Buell JS, Dawson-Hugues B: Vitamin D and neurocognitive dysfunction: preventing 'D'ecline? Mol Aspects Med 2008, 29:415–422.CrossRefPubMed
5.
go back to reference Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ: Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005, 29:21–20.CrossRefPubMed Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ: Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005, 29:21–20.CrossRefPubMed
6.
go back to reference Ramakrishna T: Vitamins and brain development. Physiol Res 1999, 48:175–187.PubMed Ramakrishna T: Vitamins and brain development. Physiol Res 1999, 48:175–187.PubMed
7.
go back to reference Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F: Vitamin D-3 and brain development. Neuroscience 2003, 118:641–653.CrossRefPubMed Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F: Vitamin D-3 and brain development. Neuroscience 2003, 118:641–653.CrossRefPubMed
8.
go back to reference de Abreu DA F, Nivet E, Baril N, Khrestchatisky M, Feron F: Developmental vitamin D deficiency alters learning in C57Bl/6J mice. Behav Brain Res 2010, 208:603–608.CrossRef de Abreu DA F, Nivet E, Baril N, Khrestchatisky M, Feron F: Developmental vitamin D deficiency alters learning in C57Bl/6J mice. Behav Brain Res 2010, 208:603–608.CrossRef
9.
go back to reference Llewellyn DJ, Langa KM, Lang IA: Serum 25-hydroxyvitamin D concentration and mild cognitive impairment. J Geriatr Psychiatry Neurol 2009, 22:188–195.CrossRefPubMed Llewellyn DJ, Langa KM, Lang IA: Serum 25-hydroxyvitamin D concentration and mild cognitive impairment. J Geriatr Psychiatry Neurol 2009, 22:188–195.CrossRefPubMed
10.
go back to reference Oudshorn C, Mattace-Raso FUS, Van der Velde N, Colin EM, Van der Cammen TJM: Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease. Dement Geriatr Cogn Disord 2008, 25:539–543.CrossRef Oudshorn C, Mattace-Raso FUS, Van der Velde N, Colin EM, Van der Cammen TJM: Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease. Dement Geriatr Cogn Disord 2008, 25:539–543.CrossRef
11.
go back to reference Llewellyn DJ, Lang IA, Langa M, Melzer D: Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci 2011, 66:59–65.CrossRefPubMed Llewellyn DJ, Lang IA, Langa M, Melzer D: Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci 2011, 66:59–65.CrossRefPubMed
12.
go back to reference Annweiler C, Schott AM, Rolland Y, Blain H, Herrmann FR, Beauchet O: Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology 2010, 75:1810–1816.CrossRefPubMed Annweiler C, Schott AM, Rolland Y, Blain H, Herrmann FR, Beauchet O: Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology 2010, 75:1810–1816.CrossRefPubMed
13.
go back to reference Annweiler C, Fantino B, Schott AM, Krolak-Salmon P, Allali G, Beauchet O: Vitamin D insufficiency and mild cognitive impairment: cross-sectional association. Eur J Neurol 2012, 19:1023–1029.CrossRefPubMed Annweiler C, Fantino B, Schott AM, Krolak-Salmon P, Allali G, Beauchet O: Vitamin D insufficiency and mild cognitive impairment: cross-sectional association. Eur J Neurol 2012, 19:1023–1029.CrossRefPubMed
14.
go back to reference Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O: Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 2009, 6:1083–1089.CrossRef Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O: Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 2009, 6:1083–1089.CrossRef
15.
go back to reference Buell JS, Scott TM, Dawson-Hughes B, Dallal GE, Rosenberg IH, Folstein MF, Tucker KL: Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci 2009, 64:888–895.CrossRefPubMed Buell JS, Scott TM, Dawson-Hughes B, Dallal GE, Rosenberg IH, Folstein MF, Tucker KL: Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci 2009, 64:888–895.CrossRefPubMed
16.
go back to reference Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL: 25-hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010, 74:18–26.CrossRefPubMedPubMedCentral Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL: 25-hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010, 74:18–26.CrossRefPubMedPubMedCentral
17.
go back to reference Brown J, Bianco JI, McGrath JJ, Eyles DW: 1,25-dihydroxyvitamin D-3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003, 343:139–143.CrossRefPubMed Brown J, Bianco JI, McGrath JJ, Eyles DW: 1,25-dihydroxyvitamin D-3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003, 343:139–143.CrossRefPubMed
18.
go back to reference Dursun E, Gezen-Ak D, Yilmazer S: A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-beta and preventing the amyloid-beta induced alterations by vitamin D in cortical neurons. J Alzheimers Dis 2010, 23:207–219. Dursun E, Gezen-Ak D, Yilmazer S: A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-beta and preventing the amyloid-beta induced alterations by vitamin D in cortical neurons. J Alzheimers Dis 2010, 23:207–219.
19.
go back to reference Jamilian H, Bagherzadeh K, Nazeri Z, Hassanijirdehi M: Vitamin D, parathyroid hormone, serum calcium and phosphorus in patients with schizophrenia and major depression. Int J Psychiatry Clin Pract 2012. PMID: 22536888 Jamilian H, Bagherzadeh K, Nazeri Z, Hassanijirdehi M: Vitamin D, parathyroid hormone, serum calcium and phosphorus in patients with schizophrenia and major depression. Int J Psychiatry Clin Pract 2012. PMID: 22536888
20.
go back to reference Zhu Y, Zhou R, Yang R, Zhang Z, Bai Y, Chang F, Li L, Sokabe M, Goltzman D, Miao D, Chen L: Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25dihydroxyvitamin D3 (1,25 (OH)2 D3). Hippocampus 2012, 22:421–433.CrossRefPubMed Zhu Y, Zhou R, Yang R, Zhang Z, Bai Y, Chang F, Li L, Sokabe M, Goltzman D, Miao D, Chen L: Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25dihydroxyvitamin D3 (1,25 (OH)2 D3). Hippocampus 2012, 22:421–433.CrossRefPubMed
21.
go back to reference Alley DE, Crimmins EM, Karlamangla A, Hu P, Seeman TE: Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol Series: A: Biol Sci Med Sci 2008, 63:50–55.CrossRef Alley DE, Crimmins EM, Karlamangla A, Hu P, Seeman TE: Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol Series: A: Biol Sci Med Sci 2008, 63:50–55.CrossRef
22.
go back to reference Bermejo P, Martin-Argon S, Benedi J, Susin C, Felici E, Gil P, Ribera JM, Villar AM: Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunol Lett 2008, 117:198–202.CrossRefPubMed Bermejo P, Martin-Argon S, Benedi J, Susin C, Felici E, Gil P, Ribera JM, Villar AM: Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunol Lett 2008, 117:198–202.CrossRefPubMed
23.
24.
go back to reference Gorelick PB: Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials. Ann N Y Acad Sci 2010, 1207:155–162.CrossRefPubMed Gorelick PB: Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials. Ann N Y Acad Sci 2010, 1207:155–162.CrossRefPubMed
25.
go back to reference Briones TL, Woods J, Wadowska M, Rogozinska M: Amelioration of cognitive impairment and changes in microtubule-associated protein 2 after transient global cerebral ischemia are influenced by complex environment experience. Behav Brain Res 2006, 168:261–271.CrossRefPubMed Briones TL, Woods J, Wadowska M, Rogozinska M: Amelioration of cognitive impairment and changes in microtubule-associated protein 2 after transient global cerebral ischemia are influenced by complex environment experience. Behav Brain Res 2006, 168:261–271.CrossRefPubMed
26.
go back to reference Briones TL, Rogozinska M, Woods J: Environmental experience modulates ischemia-induced amyloidogenesis and enhances functional recovery. J Neurotrauma 2009, 24:613–625.CrossRef Briones TL, Rogozinska M, Woods J: Environmental experience modulates ischemia-induced amyloidogenesis and enhances functional recovery. J Neurotrauma 2009, 24:613–625.CrossRef
27.
go back to reference Barker GRI, Warburton EC: When is the hippocampus involved in recognition memory? J Neurosci 2011, 31:10721–10731.CrossRefPubMed Barker GRI, Warburton EC: When is the hippocampus involved in recognition memory? J Neurosci 2011, 31:10721–10731.CrossRefPubMed
28.
go back to reference Mumby DG, Gaskin S, Glenn MJ, Schramek TE, Lehmann H: Hippocampal damage and exploratory preferences in rats: memory for objects, places, and context. Learn Mem 2002, 9:49–57.CrossRefPubMedPubMedCentral Mumby DG, Gaskin S, Glenn MJ, Schramek TE, Lehmann H: Hippocampal damage and exploratory preferences in rats: memory for objects, places, and context. Learn Mem 2002, 9:49–57.CrossRefPubMedPubMedCentral
29.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 2001, 25:402–408.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 2001, 25:402–408.CrossRefPubMed
30.
go back to reference Tuohimaa P, Keisala T, Minasyan A, Cachat J, Kalueff A: Vitamin D, nervous system and aging. Psychoneuroendocrinology 2009, 34S:S278-S286.CrossRef Tuohimaa P, Keisala T, Minasyan A, Cachat J, Kalueff A: Vitamin D, nervous system and aging. Psychoneuroendocrinology 2009, 34S:S278-S286.CrossRef
31.
go back to reference Cunningham C, Campion S, Lunnon K, Murray CL, Woods JF, Deacon RM, Rawlins JN, Perry VH: Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative diseases. Biol Psychiatry 2009, 65:304–312.CrossRefPubMedPubMedCentral Cunningham C, Campion S, Lunnon K, Murray CL, Woods JF, Deacon RM, Rawlins JN, Perry VH: Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative diseases. Biol Psychiatry 2009, 65:304–312.CrossRefPubMedPubMedCentral
32.
go back to reference Yu J, Gattoni-Celli M, Zhu H, Bhat NR, Sambamurti K, Gattoni-Celli S, Kindy MS: Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice. J Alzheimers Dis 2011, 25:295–307.PubMed Yu J, Gattoni-Celli M, Zhu H, Bhat NR, Sambamurti K, Gattoni-Celli S, Kindy MS: Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice. J Alzheimers Dis 2011, 25:295–307.PubMed
33.
go back to reference McGeer E, McGeer P: Inflammatory cytokines in the CNS. CNS Drugs 1997, 7:214–287.CrossRef McGeer E, McGeer P: Inflammatory cytokines in the CNS. CNS Drugs 1997, 7:214–287.CrossRef
34.
go back to reference Apelt J, Schliebs R: Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 2001, 892:21–30.CrossRef Apelt J, Schliebs R: Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 2001, 892:21–30.CrossRef
35.
go back to reference Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, Dantzer R, Kelley KW: Interleukin-10 in the brain. Crit Rev Immunol 2001, 21:427–449.CrossRefPubMed Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, Dantzer R, Kelley KW: Interleukin-10 in the brain. Crit Rev Immunol 2001, 21:427–449.CrossRefPubMed
36.
go back to reference Szczepanik AM, Ringheim GE: IL-10 and glucocoricoid inhibit Aβ(1–42)- and lipopolysacchiride-induced pro-inflammatory cytokine and chemokine induction in the central nervous system. J Alzheimers Dis 2003, 5:105–117.PubMed Szczepanik AM, Ringheim GE: IL-10 and glucocoricoid inhibit Aβ(1–42)- and lipopolysacchiride-induced pro-inflammatory cytokine and chemokine induction in the central nervous system. J Alzheimers Dis 2003, 5:105–117.PubMed
37.
go back to reference Nalivaeva NN, Beckett C, Belyaev ND, Turner AJ: Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer's disease? J Neurochem 2012, 120:167–185.CrossRefPubMed Nalivaeva NN, Beckett C, Belyaev ND, Turner AJ: Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer's disease? J Neurochem 2012, 120:167–185.CrossRefPubMed
Metadata
Title
Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden
Authors
Teresita L Briones
Hala Darwish
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-244

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