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  • 1 Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • | 2 Institute of Chemistry, School of Medicine, University of Belgrade, Belgrade, Serbia
  • | 3 Institute of Nuclear Sciences, “Vinča”, Belgrade, Serbia
  • | 4 Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center Belgrade, Belgrade, Serbia
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Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na+/K+-ATPase and Mg2+-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0–4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

  • 1.

    Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE: The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs. Epi. Res. 51, 237247 (2002)

    • Search Google Scholar
    • Export Citation
  • 2.

    Baydar T, Papp A, Nagymajtényi L, Schulz H, Sahin G: Folate supplementation in rats: Does it cause behavioural and electrophysiological changes? Pteridines 13, 107114 (2002)

    • Search Google Scholar
    • Export Citation
  • 3.

    Bingami A, Palladini C, Venturini G: Effect of cardiazol on sodium-potassium adenosine triphosphatase of the rat brain in vivo. Brain Res. 1, 413414 (1966)

    • Search Google Scholar
    • Export Citation
  • 4.

    Brocardo PS, Budni J, Lobato KR, Kaster MP, Rodrigues AL: Antidepressant-like effect of folic acid: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. Eur. J. Pharmacol. 598, 3742 (2008)

    • Search Google Scholar
    • Export Citation
  • 5.

    Budni J, Freitas AE, Binfaré RW, Rodrigues AL: Role of potassium channels in the antidepressant-like effect of folic acid in the forced swimming test in mice. Pharmacol. Biochem. Behav. 101(1), 148154 (2012)

    • Search Google Scholar
    • Export Citation
  • 6.

    Cohen RS, Blomber F, Berzins K, Siekevitz P: The structure of postsynaptic densities isolated from dog cerebral cortex: I. Overall morphology and protein composition. J. Cell Biol. 74, 181203 (1977)

    • Search Google Scholar
    • Export Citation
  • 7.

    D’Anci KE, Rosenberg IH: Folate and brain function in the elderly. Curr. Opin. Clin. Nutr. Metab. 7, 659664 (2004)

  • 8.

    den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, Breteler MM: Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 126: 170175 (2003)

    • Search Google Scholar
    • Export Citation
  • 9.

    Djurić D, Jakovljević V, Rasic-Markovic A, Djuric A, Stanojlovic O: Homocysteine, folic acid and coronary artery disease: possible impact on prognosis and therapy. Indian J. Chest. Dis. Allied. Sci 50, 3948 (2008)

    • Search Google Scholar
    • Export Citation
  • 10.

    Greenop KR, Miller M, de Klerk NH, Scott RJ, Attia J, Ashton LJ, Dalla-Pozza L, Bower C, Armstrong BK, Milne E: Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and risk of childhood brain tumors. Nutr. Cancer 66(5), 800809 (2014)

    • Search Google Scholar
    • Export Citation
  • 11.

    Grisar T, Guillaume D, Delgado-Escueta AV: Contribution of Na+/K+-ATPase to focal epilepsy: a brief review. Epilepsy Res. 12, 141149 (1992)

    • Search Google Scholar
    • Export Citation
  • 12.

    Hamid A, Wani NA, Kaur J: New perspectives on folate transport in relation to alcoholism-induced folate malabsorption — association with epigenome stability and cancer development. FEBS J. 276, 21752191 (2009).

    • Search Google Scholar
    • Export Citation
  • 13.

    Herrmann W, Obeid R: Homocysteine: a biomarker in neurodegenerative diseases. Clin. Chem. Lab. Med. 49, 435441 (2011)

  • 14.

    Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, Shea TB, Rogers E: Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Neurobiol. Dis. 14, 3242 (2003)

    • Search Google Scholar
    • Export Citation
  • 15.

    Ho PI, Collins SC, Dhitavat S, Ortiz D, Ashline D, Rogers E, Shea TB: Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress. J. Neurochem. 78(2), 249253 (2001)

    • Search Google Scholar
    • Export Citation
  • 16.

    Horvat A, Nikezić G, Martinović JV: Estradiol binding to synaptosomal plasma membranes of rat brain regions. Experientia 51(1), 1115 (1995)

    • Search Google Scholar
    • Export Citation
  • 17.

    Hwang SY, Siow YL, Au-Yeung KK, House JOK: Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney. Am. J. Physiol. Renal. Physiol. 300(1), F189F198 (2011)

    • Search Google Scholar
    • Export Citation
  • 18.

    Hyland K, Shoffner J, Heales SJ: Cerebral folate deficiency. Inherit. Metab. Dis. 33(5), 563570 (2010)

  • 19.

    Kado DM, Karlamangla AS, Huang MH, Troen A, Rowe JW, Selhub J, Seeman TE: Homocysteine versus the vitamins folate, B12 and B6 as predictors of cognitive function in older high functioning adults: Mac Arthur studies of successful aging. Am. J. Med. 118, 161167 (2005)

    • Search Google Scholar
    • Export Citation
  • 20.

    Kim YI: Methylenetetrahydrofolate reductase polymorphisms, folate, and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis. Nutr. Rev. 58, 205217 (2000)

    • Search Google Scholar
    • Export Citation
  • 21.

    Kronenberg G, Colla M, Endres M: Folic acid, neurodegenerative and neuropsychiatric disease. Curr. Mol. Med. 9(3), 315323 (2009)

  • 22.

    Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP: Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity J. Neurosci. 20, 69206926 (2000)

    • Search Google Scholar
    • Export Citation
  • 23.

    Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K: Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am. J. Clin. Nutr. 79, 473478 (2004)

    • Search Google Scholar
    • Export Citation
  • 24.

    Lees GJ, Leong W: Brain lesions induced by specific and non-specific inhibitors of sodium-potassium ATPase. Brain Res. 649(1–2), 225233 (1994)

    • Search Google Scholar
    • Export Citation
  • 25.

    Lees GJ: Contributory mechanisms in the causation of neurodegenerative disorders. Neurosci. 54, 287322 (1993)

  • 26.

    Lin Y, Desbois A, Jiang S, Hou ST: Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity. Neuroreport 224, 14 (2004)

    • Search Google Scholar
    • Export Citation
  • 27.

    Markovic AR, Hrnčić D, Macut D, Stanojlović O, Djuric D: Anticonvulsive effect of folic acid in homocysteine thiolactone-induced seizures. Cell. Mol. Neurobiol. 31(8), 12211228 (2011)

    • Search Google Scholar
    • Export Citation
  • 28.

    Mastropaolo D, Camerman A, Camerman N: Folic acid: crystal structure and implications for enzyme binding. Science 210(4467), 334336 (1980)

    • Search Google Scholar
    • Export Citation
  • 29.

    Mattson MP, Kruman II, Duan W: Folic acid and homocysteine in age-related disease. Ageing Res. Rev. 1, 95111 (2002)

  • 30.

    Morris MS: Folate, homocysteine, and neurological function. Nutr. Clin. Care 5(3), 124132 (2002)

  • 31.

    Nazki FH, Sameer AS, Ganaie BA: Folate: metabolism, genes, polymorphisms and the associated diseases. Gene 533(1), 1120 (2013)

  • 32.

    Niu J, Wang A, Ke Z, Zheng Z: Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating. J. Drug Target 22(8), 712723 (2014)

    • Search Google Scholar
    • Export Citation
  • 33.

    Obeid R, Hermann W: The emerging role of unmetabolized folic acid in human diseases: myth or reality? Curr. Drug Metab. 13(8), 11841195 (2012)

    • Search Google Scholar
    • Export Citation
  • 34.

    Perla-Kajan J, Twardowski T, Jakubowski H: Mechanisms of homocysteine toxicity in humans. Amino Acids 32, 561572 (2007)

  • 35.

    Picciano MF, McGuire MK: Use of dietary supplements by pregnant and lactating women in North America. Am. J. Clin. Nutr. 89(2), 663S667S (2009)

    • Search Google Scholar
    • Export Citation
  • 36.

    Rasić-Marković A, Stanojlović O, Hrncić D, Krstić D, Colović M, Susić V, Radosavljević T, Djuric D: The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol. Cell. Biochem. 327(1–2), 3915 (2009).

    • Search Google Scholar
    • Export Citation
  • 37.

    Reynolds E: Benefits and risks of folic acid to the nervous system. J. Neurol. Neurosurg. Psychiatry 72(5), 567571 (2002)

  • 38.

    Rydlewicz A, Simpson JA, Taylor RJ, Bond CM, Golden MH: The effect of folic acid supplementation on plasma homocyteine in an elderly population. Quart. J. Med. 95, 2735 (2002)

    • Search Google Scholar
    • Export Citation
  • 39.

    Sachdev PS: Homocysteine and brain atrophy. Prog. Neuropsychopharmacol. Biol. Psychiatry 29, 11521161 (2005)

  • 40.

    Sarna LK, Wu N, Wang P, Hwang SY, Siow YL: Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase. Can. J. Physiol. Pharmacol. 90(2), 155165 (2012)

    • Search Google Scholar
    • Export Citation
  • 41.

    Scott TM, Tucker KL, Bhadelia A, Benjamin B, Patz S, Bhadelia R, Liebson E, Price LL, Griffith J, Rosenberg I, Folstein MF: Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders. Am. J. Geriatr. Psychiatry 12, 631638 (2004).

    • Search Google Scholar
    • Export Citation
  • 42.

    Stanojlović O, Rasić-Marković A, Hrncić D, Susić V, Macut D, Radosavljević T, Djuric D: Two types of seizures in homocysteine thiolactone-treated adult rats, behavioral and electroencephalographic study. Cell. Mol. Neurobiol. 29, 329339 (2009)

    • Search Google Scholar
    • Export Citation
  • 43.

    Streck EL, Zugno A, Tagliari B, Wannmacher C, Wajner M, Wyse AT: Inhibition of Na+/K+-ATPase activity by the metabolites accumulating in homocystinuria. Metab. Brain Dis. 17, 8391 (2002)

    • Search Google Scholar
    • Export Citation
  • 44.

    Tagliari B, Zamin L, Salbego CG, Netto CA, Wyse AT: Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid. Int. J. Dev. Neurosci. 24(4), 285291 (2006)

    • Search Google Scholar
    • Export Citation
  • 45.

    Tjiattas L, Ortiz DO, Dhivant S, Mitton K, Rogers E, Shea TB: Folate deficiency and homocysteine induce toxicity in cultured dorsal root ganglion neurons via cytosolic calcium accumulation. Aging Cell 3(2), 7176 (2004)

    • Search Google Scholar
    • Export Citation
  • 46.

    Towle AC, Sze PY: Inactivation by Na+, K+-ATPase of cytosol glucocorticoid receptors from rat brain and liver. Mol. Cell. Biochem. 52(2), 145151 (1983)

    • Search Google Scholar
    • Export Citation
  • 47.

    Wyse AT, Streck EL, Worm P, Wajner A, Ritter F, Netto CA: Preconditioning prevents the inhibition of Na+, K+-ATPase activity after brain ischemia. Neurochem. Res. 25, 969973 (2000)

    • Search Google Scholar
    • Export Citation
  • 48.

    Vasić V, Jovanović D, Krstić D, Nikezić G, Horvat A, Vujisić L, Nedeljković N: Prevention and recovery of CuSO4-induced inhibition of Na+/K+-ATPase in rat brain synaptosomes by EDTA. Toxicol. Lett. 110, 95104 (1999)

    • Search Google Scholar
    • Export Citation
  • 49.

    Zeisel SH: Is maternal diet supplementation beneficial? Optimal development of infant depends on mother’s diet. Am. J. Clin. Nutr. 89(2), 685S687S (2009)

    • Search Google Scholar
    • Export Citation

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Editor(s)-in-Chief: Rosivall, László

Honorary Editor(s)-in-Chief): Monos, Emil

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Acta Physiologica Hungarica
Language English
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Founder Magyar Tudományos Akadémia
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