Vitamin B12 replacement therapy reduces induced depressive behavior in young rats
DOI:
https://doi.org/10.15448/1980-6108.2016.3.23499Keywords:
depression, vitamin B12, rats, disease models, animal, dietary supplementary feeding.Abstract
Aims: To assess whether mild vitamin B12 deficiency induces depression prior to the development of anemia, and whether vitamin B12 supplementation can act as a preventive measure against depression in young rats.
Methods: Wistar rats were divided into control group (n=11) and B12 group (n=10). The B12 group received vitamin B12 supplementation in drinking water throughout the study. In Phase 1, all animals received a pectin-supplemented diet (50g/kg) for six weeks to induce vitamin B12 depletion. After that, the Porsolt test was applied for induction and evaluation of depressive state and blood was collected for a complete blood count. In Phase 2, which lasted two weeks, pectin was removed from the diet and the same tests were applied again at the end.
Results: In both phases, erythrocyte count, hematocrit level, and hemoglobin concentration were normal, i.e., the rats did not develop anemia. The forced swim test results at the end of Phase 1 show that the B12 group exhibited shorter immobility time than the control group (0.44±0.32 vs. 0.75±0.18 minutes, p=0.024) and longer swimming time (4.64±0.27 vs. 4.32±0.28 minutes, p=0.013), indicating reduction of depressive state with vitamin B12 replacement therapy. When the groups were compared at the end of Phase 2, there was no significant difference in any of the forced swim test components.
Conclusions: Mild vitamin B12 deficiency, at a level that did not induce anemia, led to depressive state in young rats where vitamin B12 supplementation reversed the effects of vitamin depletion. Under normal nutritional circumstances, however, vitamin B12 supplementation did not have any effect on depressive state. These findings encourage further studies to investigate the associations between vitamin B12 and depression in young individuals. Moreover, this study also presents perspectives for a new experimental model of depression induced by vitamin B12 depletion.
Downloads
References
Maroto GNV. Depressão e sociedade: estudo das representações sociais da depressão em um grupo de pessoas adultas na cidade de São Carlos [tese]. [Campinas]: Universidade Estadual de Campinas; 2002. 597 p.
UMMC. University of Maryland Medical Center Depression [Internet]. Maryland [update 2015 Mar; cited 2013 Dec 20]. Available from: http://www.umm.edu
World Health Statistics 2016 [Internet]: monitoring health for the SDGs. [cited 2016 July 21]. Available from: http://www.who.int/gho/publications/world_health_statistics/2016/EN_WHS2016_Chapter6.pdf?ua=1
Gerson BMC. Análise da relação entre sintomatologia depressiva, níveis de vitamina B12 com sintomatologia em idosos longevos Instituto de Geriatria e Gerontologia [dissertation]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul; 2009. 152 p.
Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry. 2002;159(12):2099-101. http://dx.doi.org/10.1176/appi.ajp.159.12.2099
Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008;71(11):826-32. http://dx.doi.org/10.1212/01.wnl.0000325581.26991.f2
Garibala S, Forster S. Effects of dietary supplements on depressive symptoms in older patients: A randomized double-blind placebo controlled trial. Clin Nutr. 2007;26(5):545-51. http://dx.doi.org/10.1016/j.clnu.2007.06.007
Ng TP, Feng L, Niti M, Kua EH, Yap KB. Folate, vitamin B12, homocysteine, and depressive symptoms in a population sample of older Chinese adults. J Am Geriatr Soc. 2009 May;57(5):871-6.
http://dx.doi.org/10.1111/j.1532-5415.2009.02229.x
Lafer B, Vallada Filho HP. Genética e fisiopatologia dos transtornos depressivos. Rev Bras Psiquiatr. 1999;21 Suppl 1:S12-7. http://dx.doi.org/10.1590/S1516-44461999000500004
Perito MES, Fortunato JJ. Marcadores biológicos da depressão: uma revisão sobre a expressão de fatores neurotróficos. Rev Neurocienc. 2012;20(4):597-603.
Lopes MRA, Ribeiro JP, Ores LC, Jansen K, Souza LDM, Pinheiro RT, Silva RA. Depressão e qualidade de vida em jovens de 18 a 24 anos no sul do Brasil. Rev Psiquiatr. 2011;33(2):103-8. http://dx.doi.org/10.1590/s0101-81082011005000001
Choi S, Friso S, Ghandour H, Bagley PJ, Selhub J, Mason JB. Vitamin B12: deficiency induces anomalies of base substitution and methylation in the DNA of rat colonic epithelium. J Nutr. 2004 Apr;134(4):750-5.
Kumar KA, Lalitha A, Pavithra D, Padmavathi IJ, Ganeshan M, Rao KR Venu L, Balakrishna N, Shanker NH, Reddy SU, Chandak GR, Sengupta S, Raghunath M. Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring. J Nutr Biochem. 2013 Jan;24(1):25-31. http://dx.doi.org/10.1016/j.jnutbio.2012.01.004
National Research Council (US) Subcommittee on Laboratory Animal Nutrition. Nutrient Requirements of Laboratory Animals. 4th ed. Washington (DC): National Academies Press (US); 1995.
Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977 Apr 21;266(5604):730-2. http://dx.doi.org/10.1038/266730a0
Duarte MB, Rego MAV. Comorbidade entre depressão e doenças clínicas em um ambulatório de geriatria. Cad Saude Publica. 2007 Mar;23(3):691-700. http://dx.doi.org/10.1590/S0102-311X2007000300027
Reppold CT, Hutz CS. Prevalência de indicadores de depressão entre adolescentes no Rio Grande do Sul. Aval Psicol. 2003;2(2):175-84.
FMUSP. Centro de Bioterismo. Diretoria Técnica de Apoio ao Ensino e Pesquisa. [Internet]. [cited 2013 Mar 21]. Available from: http://www.biot.fm.usp.br/index.php?mpg=03.00.00&tip=RATO&id_ani=17&pes_idade=si
Carvalho GD, Masseno APB, Zanini MS, Zanini SF, Porfirio, LC, Machado JP, Mauad H. Avaliação clínica de ratos de laboratório (Rattus norvegicus linhagem Wistar): parâmetros sanitários, biológicos e fisiológicos. Rev Ceres. 2009;56(1):51-7.
Syed EU, Wasay M, Awan S. Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial. Open Neurol J. 2013 Nov 15;7:44-8. http://dx.doi.org/10.2174/1874205X01307010044
Paniz C, Grotto D, Schmitt GC, Valentini J, Schott KL, Pomblum VJ, Garcia SC. Fisiopatologia da deficiência de vitamina B12 e seu diagnóstico laboratorial. J Bras Patol Med Lab. 2005;41(5):323-34. http://dx.doi.org/10.1590/S1676-24442005000500007
Fábregas BC, Vitorino FD, Teixeira AL. Deficiência de vitamina B12 e transtorno depressivo. J Bras Psiquiatr. 2011;60(2):141-3.
Seppälä J, Koponen H, Kautiainen H, Eriksson JG, Kampman O, Leiviskä J, Männistö S, Mäntyselka P, Oksa H, Ovaskainen Y, Viikki M, Vanhala M. Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry. 2013 May 24;13:145. http://dx.doi.org/10.1186/1471-244X-13-145
Fernandes EV, Ramos SP, Estanislau C, Venancio EJ. Efeitos comportamentais e imunológicos da fluoxetina em ratos submetidos ao nado forçado. Psic: Teor e Pesq. 2012;4(28):409-15. http://dx.doi.org/10.1590/s0102-37722012000400008
Branco ACS, Diniz MFFM, Almeida RN, Santos HB, Oliveira KM, Ramalho JA, Dantas JG. Parâmetros bioquímicos e hematológicos de ratos Wistar e camundongos Swiss do biotério professor Thomas George. Rev Bras Cienc Saúde. 2011;15(2):209-14. http://dx.doi.org/10.4034/RBCS/2011.15.02.11
Lima CM, Lima AK, Melo MGD, Dória GAA, Serafini MR, Albuquerque-Júnior, RLC, Araújo AAS. Valores de referência hematológicos e bioquímicos de ratos (Ratus novergicus linhagem Wistar) provenientes do biotério da Universidade Tiradentes. Scientia Plena. 2014;10(3):1-9.
Tomich BP, Rocha RDR, Ferreira MFR. Anemia megaloblástica. Pós Rev [Internet]. 2012 [cited 2016];(6). Available from: http://blog.newtonpaiva.br/pos/e6-farm22-anemia-megaloblastica/
Cullen RW, Oace SM. Dietary pectin shortens the biologic half-life of vitamin B-12 in rats by increasing fecal and urinary losses. J Nutr. 1989 Aug;119(8):1121-7.
Costa-Nunes JP, Cline BH, Araújo-Correia M, Valença A, Markova N, Dolgov O, Kubatiev A, Yeritsyan N, Steinbusch HW, Strekalova T. Animal models of depression and drug delivery with food as an effective dosing method: evidences from studies with celecoxib and dicholine succinate. Biomed Res Int. 2015;2015:596126. http://dx.doi.org/10.1155/2015/596126
Vieira N, Rodríguez-Vera J, Arez L, Tomé R. Síndrome depressiva como apresentação de uma Anemia Perniciosa. Med Int. 2004;11(1):13-16.
Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;(4):CD004514. http://dx.doi.org/10.1002/14651858.cd004514
Parletta N, Milte CM, Meyer BJ. Nutritional modulation of cognitive function and mental health. J Nutr Biochem. 2013 May;24(5):725-43. http://dx.doi.org/10.1016/j.jnutbio.2013.01.002
Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry. 2002 Dec;159(12):2099-101. http://dx.doi.org/10.1176/appi.ajp.159.12.2099
Dovichi SS, Lajolo FM. Flavonoides e sistema nervoso central. Nutrire 2011;36(2):123-35.
Downloads
Published
How to Cite
Issue
Section
License
Copyright
The submission of originals to Scientia Medica implies the transfer by the authors of the right for publication. Authors retain copyright and grant the journal right of first publication. If the authors wish to include the same data into another publication, they must cite Scientia Medica as the site of original publication.
Creative Commons License
Except where otherwise specified, material published in this journal is licensed under a Creative Commons Attribution 4.0 International license, which allows unrestricted use, distribution and reproduction in any medium, provided the original publication is correctly cited.
