Abstract
In the present study we developed a chemically induced experimental model for gestational hypermethioninemia in rats and evaluated in the offspring the activities of Na+,K+-ATPase and Mg2+-ATPase, as well as oxidative stress parameters, namely sulfhydryl content, thiobarbituric acid-reactive substances and the antioxidant enzymes superoxide dismutase and catalase in encephalon. Serum and encephalon levels of methionine and total homocysteine were also evaluated in mother rats and in the offspring. Pregnant Wistar rats received two daily subcutaneous injections of methionine throughout the gestational period (21 days). During the treatment, a group of pregnant rats received dose 1 (1.34 μmol methionine/g body weight) and the other one received dose 2 (2.68 μmol methionine/g body weight). Control group received saline. After the rats give birth, a first group of pups was killed at the 7th day of life and the second group at the 21th day of life for removal of serum and encephalon. Mother rats were killed at the 21th day postpartum for removal of serum and encephalon. Both doses 1 and 2 increased methionine levels in encephalon of the mother rats and dose 2 increased methionine levels in encephalon of the offspring. Maternal hypermethioninemia also decreased the activities of Na+,K+-ATPase, Mg2+-ATPase and catalase, as well as reduced total sulfhydryl content in the encephalon of the pups. This chemical model seems to be appropriate for studies aiming to investigate the effect of maternal hypermethioninemia on the developing brain during gestation in order to clarify possible neurochemical changes in the offspring.
References
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Aksenov MY, Markesbery WR (2001) Change in thiol content and expression of glutathione redox system gene in the hippocampus and cerebellum in Alzheimer’s disease. Neurosci Lett 302:141–145
Banerjee U, Dasgupta A, Rout JK, Singh OP (2012) Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatr 37:56–61
Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Cannon SC (2004) Paying the price at the pump: dystonia from mutations in a Na+/K+-ATPase. Neuron 43:153–154
Carageorgiou H, Sideris AC, Messari I, Liakou CI, Tsakiris S (2008) The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na, K)-, Mg-ATPase activities, antioxidant status, and learning performance of aged rats. Neuropsychiatr Dis Treat 4:687–699
Chamberlin ME, Ubagai T, Mudd SH, Wilson WG, Leonard JV, Chou JY (1996) Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J Clin Invest 98:1021–1027
Chan KM, Delfert D, Junger JK (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375–380
Couce ML, Bóveda MD, García-Jimémez C, Balmaseda E, Vives I, Castiñeiras DE, Fernández-Marmiesse A, Fraga JM, Mudd SH, Corrales FJ (2013) Clinical and metabolic findings in patients with methionine adenosyltransferase I/III deficiency detected by newborn screening. Mol Genet Metab 110:218–221
da Cunha AA, Ferreira AG, da Cunha MJ, Pederzolli CD, Becker DL, Coelho JG, Dutra-Filho CS, Wyse AT (2011) Chronic hyperhomocysteinemia induces oxidative damage in the rat lung. Mol Cell Biochem 358:153–160
de Carvalho AP, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ (2004) Mutations in the Na+/K+-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 43:169–175
de Franceschi ID, Rieger E, Vargas AP, Rojas DB, Campos AG, Rech VC, Feksa LR, Wannmacher CM (2013) Effect of leucine administration to female rats during pregnancy and lactation on oxidative stress and enzymes activities of phosphoryltransfer network in cerebral cortex and hippocampus of the offspring. Neurochem Res 38:632–643
Dimenstein R, Trugo NMF, Donangelo CM, Trugo LC, Anastácio AS (1996) Effest of subadequate maternal vitamin A status on placental transfer of retinol and beta-carotene to the human fetus. Biol Neonate 69:230–234
Halliwell B (2001) Role of free radicals in the neurodegenerative diseases. Therapeutic implications for antioxidant treatment. Drugs Aging 18:685–716
Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, New York
Huether G, Thömke F, Adler L (1992) Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring. Brain Res Dev Brain Res 68:175–181
Johnson SW, Seutin V, North RA (1992) Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump. Science 258:665–667
Joseph MH, Marsden CA (1986) Amino acids and small peptides. In: Lim CK (ed) HPLC of small peptides, 1st edn. IRL Press, Oxford, pp 13–27
Kolling J, Scherer EB, da Cunha AA, da Cunha MJ, Wyse AT (2011) Homocysteine induces oxidative-nitrative stress in heart of rats: prevention by folic acid. Cardiovasc Toxicol 11:67–73
Lees GJ (1991) Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res 16:283–300
Lees GJ (1993) Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322
Lowry OH, Rosebrough NJ, Farr AL, Randal RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275
Mabry CC, Denniston JC, Nelson TL, Son CD (1963) Maternal phenylketonuria. A cause of mental retardation in children without the metabolic defect. N Engl J Med 269:1404–1408
Magera MJ, Lacey JM, Casetta B, Rinaldo P (1999) Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electrospray tandem mass spectrometry. Clin Chem 45:1517–1522
Marklund SL (1985) Pyrogallol Autoxidation. In: Greenwald RA (ed) Handbook of methods for oxygen radical research, 4th edn. CRC Press, Boca Raton, pp 243–247
Mishra OP, Delivoria-Papadopoulos M, Cahillane G, Wagerle LC (1989) Lipid peroxidation as the mechanism of modification of the affinity of Na+, K+-ATPase active sites for ATP, K+, Na+, and strophanthidin in vitro. Neurochem Res 14:845–851
Mizumori SJ, Sakai DH, Rosenzweig MR, Bennett EL, Wittreich P (1987) Investigations into the neuropharmacological basis of temporal stages of memory formation in mice trained in an active avoidance task. Behav Brain Res 23:239–250
Mudd SH (2011) Hypermethioninemias of genetic and non-genetic origin: a review. Am J Med Genet C: Semin Med Genet 157:3–32
Mudd SH, Jenden DJ, Capdevila A, Roch M, Levy HL, Wagner C (2000) Isolated hypermethioninemia: measurements of S-adenosylmethionine and choline. Metabolism 49:1542–1547
Mudd SH, Levy HL, Kraus JP (2001) Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 2007–2056
Mudd SH, Braverman N, Pomper M, Tezcan K, Kronick J, Jayakar P, Garganta C, Ampola MG, Levy HL, McCandless SE, Wiltse H, Stabler SP, Allen RH, Wagner C, Borschel MW (2003) Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap. Mol Genet Metab 79:6–16
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Sanui H, Rubin H (1982) The role of magnesium in cell proliferation and transformation. In: Boynton AL, McKeehan WL, Whitfield JP (eds) Ions, cell proliferation and cancer. Academic Pr, New York, pp 517–537
Sato T, Tanaka K, Ohnishi Y, Teramoto T, Irifune M, Nishikawa T (2004) Effects of steroid hormones on (Na+, K+)-ATPase activity inhibition-induced amnesia on the step-through passive avoidance task in gonadectomized mice. Pharmacol Res 49:151–159
Stefanello FM, Matté C, Scherer EB, Wannmacher CM, Wajner M, Wyse AT (2006) Chemically induced model of hypermethioninemia in rats. J Neurosci Methods 160:1–4
Stefanello FM, Scherer EB, Kurek AG, Mattos CB, Wyse AT (2007) Effect of hypermethioninemia on some parameters of oxidative stress and on Na+, K+-ATPase activity in hippocampus of rats. Metab Brain Dis 22:172–182
Stefanello FM, Matté C, Pederzolli CD, Kolling J, Mescka CP, Lamers ML, de Assis AM, Perry ML, dos Santos MF, Dutra-filho CS, Wyse AT (2009) Hypermethioninemia provokes oxidative damage and histological changes in liver of rats. Biochimie 91:961–968
Stefanello FM, Ferreira AG, Pereira TC, da Cunha MJ, Bonan CD, Bogo MR, Wyse AT (2011) Acute and chronic hypermethioninemia alter Na+K+-ATPase activity in rat hippocampus: prevention by antioxidants. Int J Dev Neurosci 29:483–488
Streck EL, Matté C, Vieira PS, Rombaldi F, Wannmacher CM, Wajner M, Wyse AT (2002) Reduction of Na+, K+-ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochem Res 27:1593–1598
Underwood BA (1994) Maternal vitamin A status and its importance in infancy an early childhood. Am J Clin Nutr 59:517S–524S
Vaillend C, Mason SE, Cuttle MF, Alger BE (2002) Mechanisms of neuronal hyperexcitability caused by partial inhibition of Na+-K+-ATPases in the rat CA1 hippocampal region. J Neurophysiol 88:2963–2978
Viani P, Cervato G, Fiorilli A, Cestaro B (1991) Age-related differences in synaptosomal peroxidative damage and membrane properties. J Neurochem 56:253–258
Winterbourn CC, Hampton MB (2008) Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 45:549–561
Wyse AT, Streck EL, Worm P, Wajner A, Ritter F, Netto CA (2000) Preconditioning prevents the inhibition of Na+, K+-ATPase activity after brain ischemia. Neurochem Res 25:971–975
Yufu K, Itho T, Edamatsu R, Mori A, Hirakawa M (1993) Effect of hyperbaric oxygenation on the Na+, K+-ATPase and membrane fluidity of cerebrocortical membranes after experimental subarachnoid hemorrhage. Neurochem Res 16:1033–1039
Zhan H, Tada T, Nakazato F, Tanaka Y, Hongo K (2004) Spatial learning transiently disturbed by intraventricular administration of ouabain. Neurol Res 26:35–40
Zhang LN, Sun YJ, Pan S, Li JX, Qu YE, Li Y, Wang YL, Gao ZB (2013) Na+ -K+ -ATPase, a potent neuroprotective modulator against Alzheimer disease. Fundam Clin Pharmacol 27:96–103
Acknowledgments
This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, RS, Brazil).
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schweinberger, B.M., Schwieder, L., Scherer, E. et al. Development of an animal model for gestational hypermethioninemia in rat and its effect on brain Na+,K+-ATPase/Mg2+-ATPase activity and oxidative status of the offspring. Metab Brain Dis 29, 153–160 (2014). https://doi.org/10.1007/s11011-013-9451-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-013-9451-x