Skip to main content

Advertisement

Log in

Chemically induced acute model of sarcosinemia in wistar rats

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

In the present study, we developed an acute chemically induced model of sarcosinemia in Wistar rats. Wistar rats of 7, 14 and 21 postpartum days received sarcosine intraperitoneally in doses of 0.5 mmol/Kg of body weight three time a day at intervals of 3 h. Control animals received saline solution (NaCl 0.85 g%) in the same volume (10 mL/Kg of body weight). The animals were killed after 30 min, 1, 2, 3 or 6 h after the last injection and the brain and the blood were collected for sarcosine measurement. The results showed that plasma and brain sarcosine concentrations achieved levels three to four times higher than the normal levels and decreased in a time-dependent way, achieving normal levels after 6 hours. Considering that experimental animal models are useful to investigate the pathophysiology of human disorders, our model of sarcosinemia may be useful for the research of the mechanisms of neurological dysfunction caused by high tissue sarcosine levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bar-Joseph I, Pras E, Reznik-Wolf H, et al. (2012) Mutations in the sarcosine dehydrogenase gene in patients with sarcosinemia. Hum Genet 131:1805–1810

    Article  CAS  PubMed  Google Scholar 

  • Bayer SA, Altman J (1995) Principles of neurogenesis, neuronal migration, and neural circuit formation. In: Paxinos G (ed) The rat nervous system, 3rd edn. Academic Press, San Diego, pp. 1079–1098

    Google Scholar 

  • Bayer SA, Altman J, Russo RJ, Zhang X (1993) Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14:83–144

    CAS  PubMed  Google Scholar 

  • Bergeron F, Otto A, Blache P, Day R, Denoroy L, Brandsch R, Bataille D (1998) Molecular cloning and tissue distribution of rat sarcosine dehydrogenase. Eur J Biochem 257:556–561

    Article  CAS  PubMed  Google Scholar 

  • Bridi R, Fontella FU, Pulrolnik V, Braun CA, Zorzi GK, Coelho D, Wajner M, Vargas CR, Dutra-Filho CS (2006) A chemically-induced acute model of maple syrup urine disease in rats for neurochemical studies. J Neurosci Meth 155:224–230

    Article  CAS  Google Scholar 

  • Brusque AM, Mello CF, Buchanan DN, Terraciano ST, Rocha MP, Vargas CR (1999) Effect of chemically induced propionic acidemia on neurobehavioural development of rats. Pharmacol Biochem Behav 64:529–534

    Article  CAS  PubMed  Google Scholar 

  • Cicero TJ, Adams ML, Giordano A, Miller BT, O’Connor L, Nock B (1990) Influence of morphine exposure during adolescence on the sexual maturation of male rats and the development of their offspring. J Pharmacol Exp Ther 256:1086–1093

    Google Scholar 

  • Clark JB, Bates TE, Cullingford T, Land JM (1993) Development of enzymes of energy metabolism in the neonatal mammalian brain. Dev Neurosci 15:174–180

    Article  CAS  PubMed  Google Scholar 

  • Deutsch SI, Rosse RB, Long KD, Gaskins B, Mastropaolo J (2006) Rare neurodevelopmental abnormalities of sarcosinemia may involve glycinergic stimulation of a primed N-methyl-d-aspartate receptor. Clin Neuropharmacol 29:361–363

    Article  CAS  PubMed  Google Scholar 

  • Dutra JC, Wajner M, Wannmacher CMD, Wannmacher LE, Pires RF, Rosa-Junior A (1991) Effect of postnatal methylmalonate administration on adult rat behavior. Braz J Med Biol Res 24:595–605

    CAS  PubMed  Google Scholar 

  • Enesco M, Leblond CP (1962) Increase in cell number as a factor in the growth of the organs and tissues of the young male rat. J Embryol Exp Morphol 10:530–562

    Google Scholar 

  • Gemelli T, de Andrade RB, Rojas DB, Bonorino NF, Mazzola PN, Tortorelli LS, Funchal C, Dutra-Filho CS, Wannmacher CMD (2013) Effects of b-alanine administration on selected parameters of oxidative stress and phosphoryltransfer network in cerebral cortex and cerebellum of rats. Mol Cell Biochem 80:161–170. doi:10.1007/s11010-013-1669-8

    Article  Google Scholar 

  • Gerritsen T, Waisman HA (1966) Hypersarcosinemia: an inborn error of metabolism. N Engl J Med 275:66–69

    Article  CAS  PubMed  Google Scholar 

  • Harding CO, Williams P, Pflanzer DM, Colwell RE, Lyne PW, Wolff JA (1992) SAR: a genetic mouse model for human sarcosinemia generated by ethylnitrosourea mutagenesis. Proc Nat Acad Sci. 89: 2644–2648

  • Herdon HJ, Godfrey FM, Brown AM, Coulton S, Evans JR, Cairns WJ (2001) Pharmacological assessment of the role of the glycine transporter GlyT-1 in mediating high-affinity glycine uptake by rat cerebral cortex and cerebellum synaptosomes. Neuropharmacology 41:88–96

    Article  CAS  PubMed  Google Scholar 

  • Himwich WA (1973) Problems in interpreting neurochemical changes occurring in developing and aging animals. In: Ford DH (ed) Neurobiological effects of maturation and aging. Progress in Brain Research, Elsevier Scientific, Amsterdam, pp. 13–23

    Chapter  Google Scholar 

  • Jacobson M (1978) Histogenesis and morphogenesis of the central nervous system. In: Jacobson M (ed) Developmental neurobiology. Plenum Press, New York, pp. 57–114

    Chapter  Google Scholar 

  • Jiang Y, Cheng X, Wang C, Ma Y (2010) Quantitative determination of sarcosine and related compounds in urinary samples by liquid chromatography with tandem mass spectrometry. Anal Chem 82:9022–9027. doi:10.1021/ac1019914

    Article  CAS  PubMed  Google Scholar 

  • Kimmel CA (1998) Current approaches. In: Slikker WJr, Chang LW (ed) Developmental neurotoxicology, Academic Press, San Diego, pp 675–685

  • Kracht LW, Friese M, Herholz K, Schroeder R, Bauer B, Jacobs A, Heiss WD (2003) Methyl-[11C]- l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma. Eur J Nucl Med Mol Imaging 30:868–873

    Article  CAS  PubMed  Google Scholar 

  • Krinke G, Eisenbrandt DL (1994) In: Mohr U, Dungworth DL, Capen CC (eds) Pathobiology of the aging rat. ILSI Press, Washington DC, pp. 3–9

    Google Scholar 

  • Lopez-Corcuera B, Martinez-Maza R, Nunez E, Roux M, Supplisson S, Aragon C (1998) Differential properties of two stably expressed brain-specific glycine transporters. J Neurochem 71:2211–2219

    Article  CAS  PubMed  Google Scholar 

  • Mallorga PJ, Williams JB, Jacobson M, Marques R, Chaudhary A, Conn PJ, Pettibone DJ, Sur C (2003) Pharmacology and expression analysis of glycine transporter GlyT1 with [3 H]-(N-[3-(4′-fluorophenyl)-3-(4′phenylphenoxy)propyl])sarcosine. Neuropharmacology 45:585–593

    Article  CAS  PubMed  Google Scholar 

  • Marzo A (1997) Clinical pharmacokinetic registration file for NDA and ANDA procedures. Pharmacol Res 36:425–450

    Article  CAS  PubMed  Google Scholar 

  • Moreira JC, Wannmacher CMD, Costa SM, Wajner M (1989) Effect of proline administration on rat behavior in aversive and nonaversive tasks. Pharmacol Biochem Behav 32:885–890

    Article  CAS  PubMed  Google Scholar 

  • O’Kane RL, Hawkins RA (2003) Na + −dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier. Am J Physiol Endocrinol Metab 285:1167–1173

    Article  Google Scholar 

  • Ross EM, Gilman AG (1990) Pharmacodynamics: mechanism of drug action and the relationship between drug concentration and effect. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics, 8rd edn. Macmillan Publishing Company, New York chapter 2

    Google Scholar 

  • Schardein JL (1998) Animal/human concordance in: slikker WJr, Chang LW (ed) handbook of developmental neurotoxicology. Academic Press, San Diego, pp. 687–708

    Book  Google Scholar 

  • Schulze C, Firth JA (1992) Interendothelial junctions during blood-brain barrier development in the rat: morphological changes at the level of individual tight junctional contacts. Dev Brain Res 69:85–95

    Article  CAS  Google Scholar 

  • Scott CR (2001) Sarcosinemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. The McGraw-Hill Companies, New York, pp. 2057–2063

    Google Scholar 

  • Sgaravatti AM, Vargas BA, Zandoná BR, Deckmann KB, Rockenbach FJ, Moraes TB, Monserrat JM, Sgarbi MB, Pederzolli CD, Wyse AT, Wannmacher CM, Wajner M, Dutra-Filho CS (2008) Tyrosine promotes oxidative stress in cerebral cortex of young rats. Int J Dev Neurosci 26:551–559

    Article  CAS  PubMed  Google Scholar 

  • Skvorak KJ (2009) Animal models of maple syrup urine disease. J Inherit Metab Dis 32:229–246

    Article  CAS  PubMed  Google Scholar 

  • Smith KE, Borden LA, Hartig PR, Branchek T, Weinshank RL (1992) Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron 8:927–935

    Article  CAS  PubMed  Google Scholar 

  • Socala K, Nieoczym D, Rundfeldt C, Wlaz (2010) Effects of sarcosine, a glycine transporter type 1 inhibitor, in two mouse seizure models. Pharmacol Rep 62: 392–397

  • Stefanello FM, Matté C, Scherer EB, Wannmacher CMD, Wajner M, Wyse ATS (2007) Chemically induced model of hypermethioninemia in rats. J Neurosci Methods 160:1–4

    Article  CAS  PubMed  Google Scholar 

  • Streck EL, Matté C, Vieira PS, Rombaldi F, Wannmacher CMD, Wajner M (2002) Reduction of Na+,K + −ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochem Res 27:1593–1598

    Article  CAS  PubMed  Google Scholar 

  • Ueland PM, Midttun O, Windelberg A, Svardal A, Skalevik R, Hustad S (2007) Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry. Clin Chem Lab Med 45:1737–1745

    Article  CAS  PubMed  Google Scholar 

  • Winick M, Noble A (1965) Quantitative changes in DNA, RNA and protein during prenatal and postnatal growth in rat. Dev Biol 12:451–466

    Article  CAS  PubMed  Google Scholar 

  • Wyse ATS, Sarkis JJF, Cunha-Filho JS, Teixeira MV, Schetinger MR, Wajner M (1995) ATP diphosphohydrolase activity in synaptosomes from cerebral cortex of rats subjected to chemically induced phenylketonuria. Braz J Med Biol Res 28:643–649

    CAS  PubMed  Google Scholar 

  • Wyse ATS, Sarkis JJF, Cunha-Filho JS, Teixeira MV, Schetinger MR, Wajner M, et al. (1994) Effect of phenylalanine and its metabolites on ATP diphosphohydrolase activity in synaptosomes from rat cerebral cortex. Neurochem Res 19:1175–1180

    Article  CAS  PubMed  Google Scholar 

  • Zhang HX, Hyrc K, Thio LL (2009) The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine. J Physiol 587:3207–3220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the research grants from Programa de Núcleos de Excelência (PRONEX), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and FINEP Rede Instituto Brasileiro de Neurociência.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clovis Milton Duval Wannmacher.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Andrade, R.B., Gemelli, T., Rojas, D.B. et al. Chemically induced acute model of sarcosinemia in wistar rats. Metab Brain Dis 31, 363–368 (2016). https://doi.org/10.1007/s11011-015-9759-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-015-9759-9

Keywords

Navigation