Vitamin D as a neurosteroid affecting the developing and adult brain

Annual Review of Nutrition

Volumn 34, Issue , 2014, Pages 117-141

  Groves, Natalie J ^a   McGrath, John J ^a,b   Burne, Thomas H J ^a,b  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b Queensland Center for Mental Health Research   (Australia)

Author keywords

Animal models; Behavior; Brain development; Neurochemistry; Vitamin D

Indexed keywords

AMYLOID BETA PROTEIN; CALCIUM; DOPAMINE; NEUROSTEROID; VITAMIN D; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; NEUROPROTECTIVE AGENT;

AGING; ALZHEIMER DISEASE; AUTISM; BRAIN DEVELOPMENT; CALCIUM SIGNALING; CEREBROVASCULAR ACCIDENT; COGNITION; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DEPRESSION; EPILEPSY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HUMAN; MULTIPLE SCLEROSIS; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; TRAUMATIC BRAIN INJURY; VITAMIN D DEFICIENCY; VITAMIN D METABOLISM; VITAMIN SUPPLEMENTATION; ANIMAL; BIOLOGICAL MODEL; BRAIN; CYTOLOGY; DIET SUPPLEMENTATION; DIET THERAPY; GROWTH, DEVELOPMENT AND AGING; MENTAL DISORDERS; METABOLISM; MORTALITY; NERVE CELL; NEURODEGENERATIVE DISEASES; PATHOLOGY; PATHOPHYSIOLOGY;

ANIMALS; BRAIN; DIETARY SUPPLEMENTS; HUMANS; MENTAL DISORDERS; MODELS, BIOLOGICAL; NEURODEGENERATIVE DISEASES; NEUROGENESIS; NEURONS; NEUROPROTECTIVE AGENTS; NEUROTRANSMITTER AGENTS; VITAMIN D; VITAMIN D DEFICIENCY;

EID: 84904680470     PISSN: 01999885     EISSN: 15454312     Source Type: Book Series    
DOI: 10.1146/annurev-nutr-071813-105557     Document Type: Review

References (206)

1. Abrahams BS, Geschwind DH. 2008. Advances in autism genetics: on the threshold of a new neurobiology. Nat. Rev. Genet. 9:341-55
2. Afzal S, Bojesen SE, Nordestgaard BG. 2014. Reduced 25-hydroxyvitamin D and risk of Alzheimer's disease and vascular dementia. Alzheimer's Dement. 10:296-302
3. Altemus KL, Finger S, Wolf C, Birge SJ. 1987. Behavioral correlates of vitamin D deficiency. Physiol. Behav. 39:435-40
4. Amato R, Pinelli M, Monticelli A, MieleG, Cocozza S. 2010. Schizophrenia and vitaminDrelated genes could have been subject to latitude-driven adaptation. BMC Evol. Biol. 10:351
5. Anglin RE, Samaan Z, Walter SD,McDonald SD. 2013. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br. J. Psychiatry 202:100-7
6. Annweiler C, Herrmann FR, Fantino B, Brugg B, Beauchet O. 2012. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study. Cogn. Behav. Neurol. 25:121-27
7. Annweiler C, Llewellyn DJ, Beauchet O. 2013. Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J. Alzheimer's Dis. 33:659-74
8. Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, et al. 2012. Higher vitamin D dietary intake is associated with lower risk of Alzheimer's disease: a 7-year follow-up. J. Gerontol. A Biol. Sci. Med. Sci. 67:1205-11
9. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. 2010. Vitamin D: modulator of the immune system. Curr. Opin. Pharmacol. 10:482-96
10. Baksi SN, Hughes MJ. 1982. Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Res. 242:387-90
11. Balden R, Selvamani A, Sohrabji F. 2012. Vitamin D deficiency exacerbates experimental stroke injury and dysregulates ischemia-induced inflammation in adult rats. Endocrinology 153:2420-35
12. Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, et al. 2012. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 79:1397-405
13. Barchetta I, Carotti S, Labbadia G, Gentilucci UV, Muda AO, et al. 2012. Liver vitamin D receptor, CYP2R1, and CYP27A1 expression: relationship with liver histology and vitamin D3 levels in patients with nonalcoholic steatohepatitis or hepatitis C virus. Hepatology 56:2180-87
14. Becker A, Eyles DW, McGrath JJ, Grecksch G. 2005. Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav. Brain Res. 161:306-12
15. Beecham GW, Martin ER, Li YJ, Slifer MA, Gilbert JR, et al. 2009. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am. J. Hum. Genet. 84:35-43
16. Bikle D. 2009. Nonclassic actions of vitamin D. J. Clin. Endocrinol. Metab. 94:26-34
17. Bonnet AM, Houeto JL. 1999. Pathophysiology of Parkinson's disease. Biomed. Pharmacother. 53:117-21
18. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, et al. 2008. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29:726-76
19. Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NM. 2001. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J. Neurosci. 21:98-108
20. BrionesTL, Darwish H. 2012. VitaminDmitigates age-related cognitive decline through themodulation of pro-inflammatory state and decrease in amyloid burden. J. Neuroinflamm. 9:244
21. Brondum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M. 2013. 25-Hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann. Neurol. 73:38-47
22. Brown J, Bianco JI, McGrath JJ, Eyles DW. 2003. 1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci. Lett. 343:139-43
23. Brown TH, Chapman PF, Kairiss EW, Keenan CL. 1988. Long-term synaptic potentiation. Science 242:724-28
24. Buell JS, Scott TM, Dawson-Hughes B, Dallal GE, Rosenberg IH, et al. 2009. Vitamin D is associated with cognitive function in elders receiving home health services. J. Gerontol. A Biol. Sci. Med. Sci. 64:888-95
25. Burket R, McGrath J, Eyles D. 2003. VitaminDreceptor expression in the embryonic rat brain. Neurosci. Res. Commun. 33:63-71
26. Burne TH, Becker A, Brown J, Eyles DW, Mackay-Sim A, McGrath JJ. 2004. Transient prenatal vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav. Brain Res. 154:549-55
27. Burne TH, Feron F, Brown J, Eyles DW, McGrath JJ, Mackay-Sim A. 2004. Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle. Physiol. Behav. 81:651-55
28. Byrne JH, Voogt M, Turner KM, Eyles DW, McGrath JJ, Burne TH. 2013. The impact of adult vitaminDdeficiency on behaviour and brain function in male Sprague-Dawley rats. PLoS ONE 8:e71593
29. Cantorna MT,Hayes CE, DeLucaHF. 1996. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc. Natl. Acad. Sci. USA 93:7861-64
30. Cantorna MT,WoodwardWD, Hayes CE, DeLuca HF. 1998. 1,25-Dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J. Immunol. 160:5314-19
31. Cass WA, Peters LE, Fletcher AM, Yurek DM. 2012. Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats. Neurochem. Int. 60:186-91
32. Cass WA, Smith MP, Peters LE. 2006. Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine. Ann. N. Y. Acad. Sci. 1074:261-71
33. Cekic M, Cutler SM, VanLandingham JW, Stein DG. 2011. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats. Neurobiol. Aging 32:864-74
34. Chao MV. 1994. The p75 neurotrophin receptor. J. Neurobiol. 25:1373-85
35. Chen J, Olivares-Navarrete R, Wang Y, Herman TR, Boyan BD, Schwartz Z. 2010. Protein-disulfide isomerase-associated 3 (PDIA3) mediates the membrane response to 1,25-dihydroxyvitamin D3 in osteoblasts. J. Biol. Chem. 285:37041-50
36. Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, et al. 2007. Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch. Biochem. Biophys. 460:213-17
37. Christiansen C, Rodbro P, Sjo O. 1974. "Anticonvulsant action" of vitamin D in epileptic patients? A controlled pilot study. Br. Med. J. 2:258-59
38. Clemens Z, Hollo A, Kelemen A, Rasonyi G, Fabo D, et al. 2013. Seasonality in epileptic seizures. J. Neurol. Transl. Neurosci. 1:1016
39. Correale J, Ysrraelit MC,Gaitan MI. 2009. Immunomodulatory effects of vitaminDin multiple sclerosis. Brain 132:1146-60
40. Cui X, Groves NJ, Burne TH, Eyles DW,McGrath JJ. 2013. Low vitamin D concentration exacerbates adult brain dysfunction. Am. J. Clin. Nutr. 5:907-8
41. Cui X, McGrath JJ, Burne TH, Mackay-Sim A, Eyles DW. 2007. Maternal vitamin D depletion alters neurogenesis in the developing rat brain. Int. J. Dev. Neurosci. 25:227-32
42. Cui X, Pelekanos M, Burne TH, McGrath JJ, Eyles DW. 2010. Maternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon. Neurosci. Lett. 486:220-23
43. Cui X, Pelekanos M, Liu PY, Burne TH, McGrath JJ, Eyles DW. 2013. The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience 236:77-87
44. Daly RM,GagnonC, Lu ZX, Magliano DJ, DunstanDW, et al. 2012. Prevalence of vitaminDdeficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin. Endocrinol. (Oxf.) 77:26-35
45. Ding H, Dhima K, Lockhart KC, Locascio JJ, Hoesing AN, et al. 2013. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology 81:1531-37
46. Dursun E, Gezen-Ak D, Yilmazer S. 2011. 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. Alzheimer's Dis. 23:207-19
47. Dursun E, Gezen-Ak D, Yilmazer S. 2013. A new mechanism for amyloid-?induction of iNOS: vitamin D-VDR pathway disruption. J. Alzheimer's Dis. 36:459-74
48. Eisman JA, Barkla DH, Tutton PJ. 1987. Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res. 47:21-25
49. Engelsen O, Brustad M, Aksnes L, Lund E. 2005. Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem. Photobiol. 81:1287-90
50. Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha V. 2008. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch. Neurol. 65:1348-52
51. Eyles D, Almeras L, Benech P, Patatian A, Mackay-Sim A, et al. 2007. Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain. J. Steroid Biochem. Mol. Biol. 103:538-45
52. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. 2003. Vitamin D3 and brain development. Neuroscience 118:641-53
53. EylesDW, Burne TH, McGrath JJ. 2013. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitaminDand neuropsychiatric disease. Front. Neuroendocrinol. 34:47-64
54. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. 2005. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J. Chem. Neuroanat. 29:21-30
55. Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M. 2000. Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol. Rev. 52:513-56
56. Fatemi SH, Folsom TD. 2009. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr. Bull. 35:528-48
57. Fernandes de Abreu DA, Eyles D, Feron F. 2009. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 34(Suppl. 1):S265-77
58. Fernandes de Abreu DA, Ibrahim EC, Boucraut J, Khrestchatisky M, Feron F. 2010. Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers. J. Steroid Biochem. Mol. Biol. 121:250-53
59. Fernandes de Abreu DA, Landel V, Barnett AG, McGrath J, Eyles D, Feron F. 2012. Prenatal vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation. Int. J. Mol. Sci. 13:10911-19
60. Fernandes de Abreu DA, Nivet E, Baril N, KhrestchatiskyM, Roman F, Feron F. 2010. Developmental vitamin D deficiency alters learning in C57Bl/6J mice. Behav. Brain Res. 208:603-8
61. Fernell E, Barnevik-Olsson M, Bagenholm G, Gillberg C, Gustafsson S, Saaf M. 2010. Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism. Acta Paediatr. 99:743-47
62. Fisher RS, van Emde Boas W, BlumeW, Elger C, Genton P, et al. 2005. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46:470-72
63. Frim DM, Yee WM, Isacson O. 1993. NGF reduces striatal excitotoxic neuronal loss without affecting concurrent neuronal stress. Neuroreport 4:655-58
64. Frith C. 1996. Neuropsychology of schizophrenia. What are the implications of intellectual and experiential abnormalities for the neurobiology of schizophrenia? Br. Med. Bull. 52:618-26
65. Garcion E, Sindji L, Leblondel G, Brachet P, Darcy F. 1999. 1,25-Dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J. Neurochem. 73:859-66
66. GarcionE, SindjiL,Montero-Menei C, AndreC,Brachet P, DarcyF. 1998. Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia 22:282-94
67. Garcion E, Sindji L,Nataf S, Brachet P, Darcy F,Montero-Menei CN. 2003. Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous system. Acta Neuropathol. 105:438-48
68. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. 2002. New clues about vitamin D functions in the nervous system. Trends Endocrinol. Metab. 13:100-5
69. Gash DM, Zhang Z, Gerhardt G. 1998. Neuroprotective and neurorestorative properties of GDNF. Ann. Neurol. 44:S121-25
70. Gezen-Ak D, Dursun E, Bilgic B, Hanagasi H, Ertan T, et al. 2012. Vitamin D receptor gene haplotype is associated with late-onset Alzheimer's disease. Tohoku J. Exp. Med. 228:189-96
71. Gezen-Ak D, Dursun E, Yilmazer S. 2011. The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons. PLoS ONE 6:e17553
72. Girgis CM, Clifton-Bligh RJ, Mokbel N, Cheng K, Gunton JE. 2013. Vitamin D signaling regulates proliferation, differentiation and myotube size in C2C12 skeletal muscle cells. Endocrinology 155:347-57
73. GrantWB, Cannell JJ. 2013. Autism prevalence in the United States with respect to solar UV-B doses: an ecological study. Dermatoendocrinology 5:159-64
74. Grecksch G, Ruthrich H, Hollt V, Becker A. 2009. Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats. Psychoneuroendocrinology 34(Suppl. 1):S258-64
75. Griffin MD, LutzW, Phan VA, Bachman LA, McKean DJ, Kumar R. 2001. Dendritic cell modulation by 1?,25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc. Natl. Acad. Sci. USA 98:6800-5
76. Groves NJ, Kesby JP, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH. 2013. Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice. Behav. Brain Res. 241:120-31
77. Harms LR, Burne TH, Eyles DW, McGrath JJ. 2011. Vitamin D and the brain. Best Pract. Res. Clin. Endocrinol. Metab. 25:657-69
78. Harms LR, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH. 2008. Developmental vitamin D deficiency alters adult behaviour in 129/SvJ and C57BL/6J mice. Behav. Brain Res. 187:343-50
79. Harrison PJ. 1999. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122(Part 4):593-624
80. Haussler MR,Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, et al. 1998. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J. Bone Miner. Res. 13:325-49
81. Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. 2011. Vitamin D3 is more potent than vitamin D2 in humans. J. Clin. Endocrinol. Metab. 96:E447-52
82. HewisonM, Burke F, Evans KN, Lammas DA, Sansom DM, et al. 2007. Extra-renal 25-hydroxyvitamin D3-1?-hydroxylase in human health and disease. J. Steroid Biochem. Mol. Biol. 103:316-21
83. Hoang MT, Defina LF, Willis BL, Leonard DS, Weiner MF, Brown ES. 2011. Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: the Cooper Center Longitudinal Study. Mayo Clin. Proc. 86:1050-55
84. Hohman EE, Martin BR, Lachcik PJ, Gordon DT, Fleet JC, Weaver CM. 2011. Bioavailability and efficacy of vitamin D2 from UV-irradiated yeast in growing, vitamin D-deficient rats. J. Agric. Food Chem. 59:2341-46
85. Holick MF. 1995. Environmental factors that influence the cutaneous production of vitamin D. Am. J. Clin. Nutr. 61(3 Suppl.):638-45S
86. Holick MF, Binkley NC, Bischoff-Ferrari HA,Gordon CM,Hanley DA, et al. 2012. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J. Clin. Endocrinol. Metab. 97:1153-58
87. Hollo A, Clemens Z,Kamondi A, Lakatos P, Szucs A. 2012. Correction of vitaminDdeficiency improves seizure control in epilepsy: a pilot study. Epilepsy Behav. 24:131-33
88. HoogendijkWJ, Lips P, DikMG, Deeg DJ, Beekman AT, Penninx BW. 2008. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch. Gen. Psychiatry 65:508-12
89. Horst RL, Napoli JL, Littledike ET. 1982. Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick. Biochem. J. 204:185-89
90. Hua F, Reiss JI, Tang H, Wang J, Fowler X, et al. 2012. Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury. Horm. Behav. 61:642-51
91. Jiang P, Zhang WY, Li HD, Cai HL, Liu YP, Chen LY. 2013. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats. Psychoneuroendocrinology 38:2091-98
92. Jorde R, Sneve M, Figenschau Y, Svartberg J,Waterloo K. 2008. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J. Intern. Med. 264:599-609
93. Jorde R, Strand HutchinsonM, KjaergaardM, Sneve M, Grimnes G. 2013. Supplementation with high doses of vitamin D to subjects without vitamin D deficiency may have negative effects: pooled data from four intervention trials in Troms. ISRN Endocrinol. 2013:348705
94. Joseph B, Wallen-Mackenzie A, Benoit G, Murata T, Joodmardi E, et al. 2003. p57Kip2 cooperates with Nurr1 in developing dopamine cells. Proc. Natl. Acad. Sci. USA 100:15619-24
95. Kaelber CT, Moul DE, Farmer ME. 1995. Epidemiology of depression. In Handbook of Depression, ed. EE Beckham, WR Leber, pp. 3-35. New York: Guilford
96. Kampman MT, Wilsgaard T, Mellgren SI. 2007. Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J. Neurol. 254:471-77
97. Kearns CM, CassWA, Smoot K, Kryscio R, Gash DM. 1997. GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. J. Neurosci. 17:7111-18
98. Keilhoff G, Grecksch G, Becker A. 2010. Haloperidol normalized prenatal vitamin D depletion-induced reduction of hippocampal cell proliferation in adult rats. Neurosci. Lett. 476:94-98
99. Kesby JP, Burne TH, McGrath JJ, Eyles DW. 2006. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: an animalmodel of schizophrenia. Biol. Psychiatry 60:591-96
100. Kesby JP, Cui X, Burne TH, Eyles DW. 2013. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia. Front. Cell Neurosci. 7:111
101. Kesby JP, Cui X, Ko P,McGrath JJ, Burne TH, Eyles DW. 2009. Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain. Neurosci. Lett. 461:155-58
102. Kesby JP, Cui X, O'Loan J, McGrath JJ, Burne TH, Eyles DW. 2010. Developmental vitamin D deficiency alters dopamine-mediated behaviors and dopamine transporter function in adult female rats. Psychopharmacology (Berl.) 208:159-68
103. Khanal RC, Nemere I. 2007. The ERp57/GRp58/1,25D3-MARRS receptor: multiple functional roles in diverse cell systems. Curr. Med. Chem. 14:1087-93
104. Khoraminya N, Tehrani-Doost M, Jazayeri S, Hosseini A, Djazayery A. 2013. Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder. Aust. N. Z. J. Psychiatry 47:271-75
105. KinneyDK, BarchDH, Chayka B, Napoleon S,Munir KM. 2010. Environmental risk factors for autism: Do they help cause de novo genetic mutations that contribute to the disorder? Med. Hypotheses 74:102-6
106. KjaergaardM,WaterlooK,WangCE, AlmasB,FigenschauY, et al. 2012. Effect of vitaminDsupplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br. J. Psychiatry 201:360-68
107. Knekt P, Kilkkinen A, Rissanen H,Marniemi J, Saaksjarvi K, HeliovaaraM. 2010. Serum vitamin D and the risk of Parkinson disease. Arch. Neurol. 67:808-11
108. Ko P, Burkert R, McGrath J, Eyles D. 2004. Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development. Brain Res. Dev. Brain Res. 153:61-68
109. Korsching S, Auburger G, Heumann R, Scott J, Thoenen H. 1985. Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J. 4:1389-93
110. Kume T, Nishikawa H, Tomioka H, Katsuki H, Akaike A, et al. 2000. p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures. Brain Res. 852:279-89
111. Lee SJ, Lee HK, Kweon YS, Lee CT, Lee KU. 2009. The impact of executive function on emotion recognition and emotion experience in patients with schizophrenia. Psychiatry Investig. 6:156-62
112. Lefebvre d'Hellencourt C,Montero-Menei CN, Bernard R, Couez D. 2003. Vitamin D3 inhibits proinflammatory cytokines and nitric oxide production by the EOC13 microglial cell line. J. Neurosci. Res. 71:575-82
113. Lehmann B, Meurer M. 2010. Vitamin D metabolism. Dermatol. Ther. 23:2-12
114. Lemire JM, Adams JS. 1992. 1,25-DihydroxyvitaminD3 inhibits the passive transfer of cellular immunity by a myelin basic protein-specific T cell clone. J. Bone Miner. Res. 7:171-77
115. Lemire JM, Archer DC. 1991. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J. Clin. Invest. 87:1103-7
116. Lips P. 2010. Worldwide status of vitamin D nutrition. J. Steroid Biochem. Mol. Biol. 121:297-300
117. Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, et al. 2010. Vitamin D and risk of cognitive decline in elderly persons. Arch. Intern. Med. 170:1135-41
118. Llewellyn DJ, Langa KM, Lang IA. 2009. Serum 25-hydroxyvitamin D concentration and cognitive impairment. J. Geriatr. Psychiatry Neurol. 22:188-95
119. LorrM, Sonn TM, Katz MM. 1967. Toward a definition of depression. Arch. Gen. Psychiatry 17:183-86
120. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT. 2003. Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J. Neuroimmunol. 134:128-32
121. Maisonpierre PC, Belluscio L, Squinto S, IpNY, FurthME, et al. 1990. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 247:1446-51
122. Manolagas SC, Provvedini DM, Tsoukas CD. 1985. Interactions of 1,25-dihydroxyvitamin D3 and the immune system. Mol. Cell Endocrinol. 43:113-22
123. Marniemi J, Alanen E, Impivaara O, Seppanen R, Hakala P, et al. 2005. Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr. Metab. Cardiovasc. Dis. 15:188-97
124. Mayne CG, Spanier JA, Relland LM, Williams CB, Hayes CE. 2011. 1,25-Dihydroxyvitamin D3 acts directly on theTlymphocyte vitaminDreceptor to inhibit experimental autoimmune encephalomyelitis. Eur. J. Immunol. 41:822-32
125. Mazdeh M, Seifirad S, Kazemi N, Seifrabie MA, Dehghan A, Abbasi H. 2013. Comparison of vitamin D3 serum levels in new diagnosed patients with multiple sclerosis versus their healthy relatives. Acta Med. Iran. 51:289-92
126. McDonald C, Murray RM. 2000. Early and late environmental risk factors for schizophrenia. Brain Res. Brain Res. Rev. 31:130-37
127. McGrath J. 1999. Hypothesis: Is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophr. Res. 40:173-77
128. McGrath J, Scragg R, Chant D, Eyles D, Burne T, Obradovic D. 2007. No association between serum 25-hydroxyvitamin D3 level and performance on psychometric tests in NHANES III. Neuroepidemiology 29:49-54
129. McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, et al. 2010. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch. Gen. Psychiatry 67:889-94
130. Meguid NA, Hashish AF, Anwar M, Sidhom G. 2010. Reduced serum levels of 25-hydroxy and 1,25- dihydroxy vitamin D in Egyptian children with autism. J. Altern. Complement. Med. 16:641-45
131. Menegaz D, Mizwicki MT, Barrientos-Duran A, Chen N, Henry HL, Norman AW. 2011. Vitamin D receptor (VDR) regulation of voltage-gated chloride channels by ligands preferring a VDR-alternative pocket (VDR-AP). Mol. Endocrinol. 25:1289-300
132. Milaneschi Y, Bandinelli S, Penninx BW, Vogelzangs N, Corsi AM, et al. 2011. Depressive symptoms and inflammation increase in a prospective study of older adults: a protective effect of a healthy (Mediterranean-style) diet. Mol. Psychiatry 16:589-90
133. Milaneschi Y, ShardellM, Corsi AM, Vazzana R, Bandinelli S, et al. 2010. Serum 25-hydroxyvitamin D and depressive symptoms in older women and men. J. Clin. Endocrinol. Metab. 95:3225-33
134. Miyaura C, Abe E, Nomura H, Nishii Y, Suda T. 1982. 1?,25- Dihydroxyvitamin D3 suppresses proliferation of murine granulocyte-macrophage progenitor cells (CFU-C). Biochem. Biophys. Res. Commun. 108:1728-33
135. Mora JR, Iwata M, von Andrian UH. 2008. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat. Rev. Immunol. 8:685-98
136. Moskovitz RA. 1978. Seasonality in schizophrenia. Lancet 1:664
137. Mostafa GA, Al-Ayadhi LY. 2012. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J. Neuroinflammation 9:201
138. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. 2007. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370:851-58
139. Mozaffari-Khosravi H, Nabizade L, Yassini-Ardakani SM, Hadinedoushan H, Barzegar K. 2013. The effect of 2 different single injections of high dose of vitamin D on improving the depression in depressed patients with vitamin D deficiency: a randomized clinical trial. J. Clin. Psychopharmacol. 33:378-85
140. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. 2006. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296:2832-38
141. Munger KL, Zhang SM, O'Reilly E, Hernan MA, OlekMJ, et al. 2004. Vitamin D intake and incidence of multiple sclerosis. Neurology 62:60-65
142. Nataf S, Garcion E, Darcy F, Chabannes D, Muller JY, Brachet P. 1996. 1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis. J. Neuropathol. Exp. Neurol. 55:904-14
143. Naveilhan P, Neveu I, BaudetC, Funakoshi H, Wion D, et al. 1996. 1,25-DihydroxyvitaminD3 regulates the expression of the low-affinity neurotrophin receptor. Brain Res. Mol. Brain Res. 41:259-68
144. Naveilhan P, Neveu I, Wion D, Brachet P. 1996. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport 7:2171-75
145. Nemere I, Garbi N, Hammerling G, Hintze KJ. 2012. Role of the 1,25D3-MARRS receptor in the 1,25(OH)2D3-stimulated uptake of calcium and phosphate in intestinal cells. Steroids 77:897-902
146. Neveu I, Naveilhan P, BaudetC, Brachet P, Metsis M. 1994. 1,25-DihydroxyvitaminD3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 6:124-26
147. Neveu I, Naveilhan P, Jehan F, Baudet C,Wion D, et al. 1994. 1,25-Dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells. Brain Res. Mol. Brain Res. 24:70-76
148. Nissou MF, Brocard J, El Atifi M, Guttin A, Andrieux A, et al. 2013. The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3 includes genes limiting the progression of neurodegenerative diseases. J. Alzheimer's Dis. 35:553-64
149. O'Gorman C, Lucas R, Taylor B. 2012. Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms. Int. J. Mol. Sci. 13:11718-52
150. Pearlson GD. 2000. Neurobiology of schizophrenia. Ann. Neurol. 48:556-66
151. Pendyala G, Ninemire C, Fox HS. 2012. Protective role for the disulfide isomerase PDIA3 in methamphetamine neurotoxicity. PLoS ONE 7:e38909
152. Peterson A, Mattek N, Clemons A, Bowman GL, Buracchio T, et al. 2012. Serum vitamin D concentrations are associated with falling and cognitive function in older adults. J. Nutr. Health Aging 16:898-901
153. Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, et al. 2008. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke 39:2611-13
154. Pols HA,Birkenhager JC, Foekens JA, vanLeeuwen JP. 1990. Vitamin D: amodulator of cell proliferation and differentiation. J. Steroid Biochem. Mol. Biol. 37:873-76
155. Pozuelo-Moyano B, Benito-Leon J,Mitchell AJ, Hernandez-Gallego J. 2013. A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis. Neuroepidemiology 40:147-53
156. Procopio M, Marriott PK. 1998. Seasonality of birth in epilepsy: a Danish study. Acta Neurol. Scand. 98:297-301
157. Procopio M, Marriott PK, Davies RJ. 2006. Seasonality of birth in epilepsy: a Southern Hemisphere study. Seizure 15:17-21
158. Procopio M, Marriott PK, Williams P. 1997. Season of birth: aetiological implications for epilepsy. Seizure 6:99-105
159. Prufer K, Barsony J. 2002. RetinoidXreceptor dominates the nuclear import and export of the unliganded vitamin D receptor. Mol. Endocrinol. 16:1738-51
160. Prufer K, Veenstra TD, Jirikowski GF, Kumar R. 1999. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord. J. Chem. Neuroanat. 16:135-45
161. Pugliatti M, Harbo HF, Holmoy T, Kampman MT, Myhr KM, et al. 2008. Environmental risk factors in multiple sclerosis. Acta Neurol. Scand. Suppl. 188:34-40
162. Quintero EM,Willis LM, Zaman V, Lee J, Boger HA, et al. 2004. Glial cell line-derived neurotrophic factor is essential for neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway. Neuroscience 124:137-46
163. Ramagopalan SV, Dyment DA, Cader MZ, Morrison KM, Disanto G, et al. 2011. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann. Neurol. 70:881-86
164. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, et al. 2010. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 20:1352-60
165. SalamiM, Talaei SA, Davari S, Taghizadeh M. 2012. Hippocampal long term potentiation in rats under different regimens of vitamin D: an in vivo study. Neurosci. Lett. 509:56-59
166. Sanchez B, Lopez-Martin E, Segura C, Labandeira-Garcia JL, Perez-Fernandez R. 2002. 1,25- Dihydroxyvitamin D3 increases striatal GDNF mRNA and protein expression in adult rats. Brain Res. Mol. Brain Res. 108:143-46
167. Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R. 2009. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J. Neurosci. Res. 87:723-32
168. Sanders KM, Stuart AL, Williamson EJ, Jacka FN, Dodd S, et al. 2011. Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Br. J. Psychiatry 198:357-64
169. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. 2005. Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients. Mov. Disord. 20:1598-603
170. Sawcer S, HellenthalG, Pirinen M, Spencer CC, Patsopoulos NA, et al. 2011. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476:214-19
171. Schrader M, Kahlen JP, Carlberg C. 1997. Functional characterization of a novel type of 1?,25- dihydroxyvitamin D3 response element identified in the mouse c-fos promoter. Biochem. Biophys. Res. Commun. 230:646-51
172. Schuster I. 2011. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim. Biophys. Acta 1814:186-99
173. Shahbeigi S, Pakdaman H, Fereshtehnejad SM, Nikravesh E,Mirabi N, Jalilzadeh G. 2013. Vitamin D3 concentration correlates with the severity of multiple sclerosis. Int. J. Prev. Med. 4:585-91
174. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B. 2011. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J. Neurol. Neurosurg. Psychiatry 82:1132-41
175. Slinin Y, Paudel ML, Taylor BC, Fink HA, Ishani A, et al. 2010. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 74:33-41
176. Sonnenberg J, Luine VN, Krey LC, Christakos S. 1986. 1,25- Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 118:1433-39
177. Stephensen CB, Zerofsky M, Burnett DJ, Lin YP, Hammock BD, et al. 2012. Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the serum of healthy adults. J. Nutr. 142:1246-52
178. Suzuki M, Yoshioka M, Hashimoto M, Murakami M, Noya M, et al. 2013. Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.Am. J. Clin.Nutr. 97:1004-13
179. Taghizadeh M, Talaei SA, Salami M. 2013. Vitamin D deficiency impairs spatial learning in adult rats. Iran. Biomed. J. 17:42-48
180. TekesK,GyengeM, Folyovich A, CsabaG. 2009. Influence of neonatal vitamin A or vitaminDtreatment on the concentration of biogenic amines and their metabolites in the adult rat brain. Horm. Metab. Res. 41:277-80
181. Tekes K, Gyenge M, Hantos M, Csaba G. 2009. Transgenerational hormonal imprinting caused by vitamin A and vitamin D treatment of newborn rats. Alterations in the biogenic amine contents of the adult brain. Brain Dev. 31:666-70
182. Tenenhouse A, Warner M, Commissiong JW. 1991. Neurotransmitters in the CNS of the vitamin D deficient, hypocalcemic rat. Neurochem. Int. 18:249-55
183. Tohda C, Urano T, UmezakiM, Nemere I, Kuboyama T. 2012. Diosgenin is an exogenous activator of 1,25D3-MARRS/Pdia3/ERp57 and improves Alzheimer's disease pathologies in 5XFAD mice. Sci. Rep. 2:535
184. Tomac A, Widenfalk J, Lin LF, Kohno T, Ebendal T, et al. 1995. Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult. Proc. Natl. Acad. Sci. USA 92:8274-78
185. Tsai MJ, O'Malley BW. 1994. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63:451-86
186. Tu WJ, Zhao SJ, Xu DJ, Chen H. 2014. Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischaemic stroke. Clin. Sci. (Lond.) 126:339-46
187. Turner KM, Young JW, McGrath JJ, EylesDW, Burne TH. 2013. Cognitive performance and response inhibition in developmentally vitamin D (DVD)-deficient rats. Behav. Brain Res. 242:47-53
188. Van Cromphaut SJ, Dewerchin M, Hoenderop JG, Stockmans I, Van Herck E, et al. 2001. Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proc. Natl. Acad. Sci. USA 98:13324-29
189. van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, et al. 2003. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 327:316
190. VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. 2004. Multiple sclerosis and vitamin D: an update. Eur. J. Clin. Nutr. 58:1095-109
191. Veenstra TD, Prufer K, Koenigsberger C, Brimijoin SW, Grande JP, Kumar R. 1998. 1,25- Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo. Brain Res. 804:193-205
192. Walbert T, Jirikowski GF, Prufer K. 2001. Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the limbic system of the rat. Horm. Metab. Res. 33:525-31
193. Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, et al. 2001. Vitamin D3 attenuates 6- hydroxydopamine-induced neurotoxicity in rats. Brain Res. 904:67-75
194. Wang L, Hara K, Van Baaren JM, Price JC, Beecham GW, et al. 2012. Vitamin D receptor and Alzheimer's disease: a genetic and functional study. Neurobiol. Aging 33:1844e1-9
195. Wang Y, Chang CF, Morales M, Chiang YH, Hoffer J. 2002. Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury. Ann. N. Y. Acad. Sci. 962:423-37
196. Wang Y, Zhu J,DeLucaHF. 2012. Where is the vitaminDreceptor? Arch. Biochem. Biophys. 523:123-33
197. Wergeland S,TorkildsenO,MyhrKM, Aksnes L, Mork SJ, Bo L. 2011. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS ONE 6:e26262
198. Williams JH, Wellman NA, Geaney DP, Cowen PJ, Feldon J, Rawlins JN. 1998. Reduced latent inhibition in people with schizophrenia: an effect of psychosis or of its treatment. Br. J. Psychiatry 172:243-49
199. Wion D, MacGrogan D, Neveu I, Jehan F, Houlgatte R, Brachet P. 1991. 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. J. Neurosci. Res. 28:110-14
200. WrightDW,Kellermann AL, HertzbergVS, Clark PL, FrankelM, et al. 2007. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann. Emerg. Med. 49:391-402.e2
201. Xiao G, Wei J, Yan W, Wang W, Lu Z. 2008. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit. Care 12:R61
202. Yasuhara T, Hara K, Maki M, Masuda T, Sanberg CD, et al. 2008. Dietary supplementation exerts neuroprotective effects in ischemic stroke model. Rejuvenation Res. 11:201-14
203. Zanatta L, Goulart PB, Goncalves R, Pierozan P, Winkelmann-Duarte EC, et al. 2012. 1?,25- dihydroxyvitamin D3 mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats. Biochim. Biophys. Acta 1823:1708-19
204. Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, et al. 2001. Extrarenal expression of 25-hydroxyvitamin D3-1?-hydroxylase. J. Clin. Endocrinol. Metab. 86:888-94
205. Zetterstrom RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T. 1997 Dopamine neuron agenesis in Nurr1-deficient mice. Science 276 248-50
206. Zhu Y, Zhou R, Yang R, Zhang Z, Bai Y, et al. 2012. Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3). Hippocampus 22:421-33