Central and Systemic Responses to Methionine-induced Hyperhomocysteinemia in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Aug 26

PMID 25153079

Citations 11

Authors

Marina Mastelaro de Rezende

Vania DAlmeida

Affiliations

Soon will be listed here.

Abstract

Hyperhomocysteinemia has been considered a risk factor for neuropsychiatric disorders, but the mechanisms involved in this process have not been completely elucidated. The aim of this study was to analyze the influence of hyperhomocysteinemia induction by methionine supplementation considering different levels and periods of exposure in mice. For this purpose, methionine supplementation at concentrations of 0.5 and 1% were administered in water to increase homocysteinemia in male C57BL/6 mice, and was maintained for 3 time periods (2, 4 and 6 months of treatment). The results from one-carbon metabolism parameters, brain-derived neurotrophic factor (BDNF) concentrations and behavioral evaluation were compared. The 0.5% supplementation was efficient in increasing plasma homocysteine levels after 2 and 6 months. The 1% supplementation, increased plasma homocysteine after 2, 4 and 6 months. Little influence was observed in cysteine and glutathione concentrations. Frontal cortex BDNF levels showed a lack of treatment influence in all periods; only the expected decrease due to increasing age was observed. Moreover, the only behavioral alteration observed using a novel object recognition task was that which was expected with increasing age. We found that responses to hyperhomocysteinemia varied based on how it was reached, and the length of toxicity. Moreover, hyperhomocysteinemia can affect the normal pattern of one carbon metabolism during age increase in mice. These findings allow the establishment of a reliable animal model for studies in this field.

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References

Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T . Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics. 2013; 8(6):584-90. PMC: 3857338. DOI: 10.4161/epi.24621. View

Dayal S, Lentz S . Murine models of hyperhomocysteinemia and their vascular phenotypes. Arterioscler Thromb Vasc Biol. 2008; 28(9):1596-605. PMC: 2574668. DOI: 10.1161/ATVBAHA.108.166421. View

Gao L, Zeng X, Guo H, Wu X, Chen H, Di R . Cognitive and neurochemical alterations in hyperhomocysteinemic rat. Neurol Sci. 2011; 33(1):39-43. DOI: 10.1007/s10072-011-0645-x. View

Ryabinin A, Miller M, Durrant S . Effects of acute alcohol administration on object recognition learning in C57BL/6J mice. Pharmacol Biochem Behav. 2002; 71(1-2):307-12. DOI: 10.1016/s0091-3057(01)00661-x. View

Topaloglu A, Sansaricq C, Snyderman S . Influence of metabolic control on growth in homocystinuria due to cystathionine B-synthase deficiency. Pediatr Res. 2001; 49(6):796-8. DOI: 10.1203/00006450-200106000-00014. View

Swart K, van Schoor N, Heymans M, Schaap L, den Heijer M, Lips P . Elevated homocysteine levels are associated with low muscle strength and functional limitations in older persons. J Nutr Health Aging. 2013; 17(6):578-84. DOI: 10.1007/s12603-013-0047-2. View

McGonigle P . Animal models of CNS disorders. Biochem Pharmacol. 2013; 87(1):140-9. DOI: 10.1016/j.bcp.2013.06.016. View

Sachdev P . Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(7):1152-61. DOI: 10.1016/j.pnpbp.2005.06.026. View

Martins P, Camargo Galdieri L, Souza F, Andersen M, Benedito-Silva A, Tufik S . Physiological variation in plasma total homocysteine concentrations in rats. Life Sci. 2005; 76(22):2621-9. DOI: 10.1016/j.lfs.2004.12.011. View

10.

Calegare B, Fernandes L, Tufik S, DAlmeida V . Biochemical, biometrical and behavioral changes in male offspring of sleep-deprived mice. Psychoneuroendocrinology. 2009; 35(5):775-84. DOI: 10.1016/j.psyneuen.2009.11.004. View

11.

Matte C, Pereira L, Dos Santos T, Mackedanz V, Cunha A, Netto C . Acute homocysteine administration impairs memory consolidation on inhibitory avoidance task and decreases hippocampal brain-derived neurotrophic factor immunocontent: prevention by folic acid treatment. Neuroscience. 2009; 163(4):1039-45. DOI: 10.1016/j.neuroscience.2009.07.023. View

12.

Lominadze D, Tyagi N, Sen U, Ovechkin A, Tyagi S . Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor. Mol Cell Biochem. 2012; 371(1-2):89-96. PMC: 3484206. DOI: 10.1007/s11010-012-1425-5. View

13.

Kapczinski F, Frey B, Andreazza A, Kauer-SantAnna M, Cunha A, Post R . Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes. Braz J Psychiatry. 2008; 30(3):243-5. DOI: 10.1590/s1516-44462008000300011. View

14.

Loas G . Vulnerability to depression: a model centered on anhedonia. J Affect Disord. 1996; 41(1):39-53. DOI: 10.1016/0165-0327(96)00065-1. View

15.

Afman L, Blom H, Drittij M, Brouns M, van Straaten H . Inhibition of transmethylation disturbs neurulation in chick embryos. Brain Res Dev Brain Res. 2005; 158(1-2):59-65. DOI: 10.1016/j.devbrainres.2005.06.002. View

16.

Szapacs M, Mathews T, Tessarollo L, Lyons W, Mamounas L, Andrews A . Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. J Neurosci Methods. 2004; 140(1-2):81-92. DOI: 10.1016/j.jneumeth.2004.03.026. View

17.

Cai B, Li X, Wang Y, Liu Y, Yang F, Chen H . Apoptosis of bone marrow mesenchymal stem cells caused by homocysteine via activating JNK signal. PLoS One. 2013; 8(5):e63561. PMC: 3646804. DOI: 10.1371/journal.pone.0063561. View

18.

Coelho C, KLEIN N . Methionine and neural tube closure in cultured rat embryos: morphological and biochemical analyses. Teratology. 1990; 42(4):437-51. DOI: 10.1002/tera.1420420412. View

19.

Refsum H, Ueland P, Nygard O, Vollset S . Homocysteine and cardiovascular disease. Annu Rev Med. 1998; 49:31-62. DOI: 10.1146/annurev.med.49.1.31. View

20.

Pfeiffer C, Huff D, Gunter E . Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin Chem. 1999; 45(2):290-2. View