Skip to main content
Log in

Equilibrated diet restores the effects of early age choline-deficient feeding on rat brain antioxidant status and enzyme activities: the role of homocysteine, l-phenylalanine and l-alanine

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

Abstract

Choline is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions, that affect the developing brain. The aim of this study was to: (a)examine the effects of early age choline deficient diet (CDD) administration on the total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+-ATPase in the rat brain, (b)investigate the effect of feeding restoration into an equilibrated diet on the above parameters, and (c)study the role of homocysteine (Hcy), l-phenylalanine (Phe) and l-alanine (Ala) in certain of the above effects. Male and female Wistar rats were continuously kept off choline (Ch) during their gestational period of life, as well as during the first 6 weeks of their post-gestational life. The animals were sacrificed by decapitation and their whole brains were rapidly removed and homogenated. Their enzyme activities were measured spectrophotometrically. Moreover, in vitro experiments were conducted in order to estimate the effects of Hcy (0.3 mM), Phe (1.2 mM) and/or Ala (1.2 mM) on the above parameters. The administration of CDD led to a statistically significant decrease of the rat brain TAS (−29%, p < 0.001) and to a significant increase of both AChE (+20%, p < 0.001) and (Na+,K+)-ATPase (+35%, p < 0.001) activities. Mg2+-ATPase activity was found unaltered. Equilibrated diet, administered to early age CDD-treated rats of both sexes for an additional period of 18 weeks, restored the above parameters to control levels. Moreover, the in vitro experiments showed that Hcy could simulate these changes (at least under the examined in vitro conditions), while both Phe and Ala act protectively against the CDD-induced effects on the examined rat brain enzyme activities. The effects of early age CDD-feeding on the examined parameters are proved to be reversible through restoration to equilibrated diet, while our data suggest a role for Hcy (as a causative parameter for the CDD-induced effects) and a possible protective role for Phe and Ala (in reversing the observed CDD-induced effects).

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

Similar content being viewed by others

References

  • Blusztajn JK (1998) Choline, a vital amine. Science 281:794–795

    Article  PubMed  CAS  Google Scholar 

  • Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221:614–620

    Article  PubMed  CAS  Google Scholar 

  • Blusztajn JK, Zeisel SH, Wurtman RJ (1985) Developmental changes in the activity of phosphatibylethanolamine N-methyltransferases in rat brain. Biochem J 232:505–511

    PubMed  CAS  Google Scholar 

  • Bogdanski DF, Tissari A, Brodie BB (1968) Role of sodium, potassium, ouabain and reserpine in uptake, storage and metabolism of biogenic amines in synaptosomes. Life Sci 7:419–428

    Article  PubMed  CAS  Google Scholar 

  • Bowler K, Tirri R (1974) The temperature characteristics of synaptic membrane ATPases from immature and adult rat brain. J Neurochem 23:611–613

    Article  PubMed  CAS  Google Scholar 

  • Carageorgiou H, Zarros A, Tsakiris S (2003) Selegiline long-term effects on brain acetylcholinesterase, (Na+,K+)-ATPase activities, antioxidant status and learning performance of aged rats. Pharmacol Res 48:245–251

    Article  PubMed  CAS  Google Scholar 

  • Carageorgiou H, Tzotzes V, Pantos C, Mourouzis C, Zarros A, Tsakiris S (2004) In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+,K+)-ATPase and Mg2+-ATPase activities: protection by l-cysteine. Basic Clin Pharmacol Toxicol 94:112–118

    Article  PubMed  CAS  Google Scholar 

  • Carageorgiou H, Pantos C, Zarros A, Mourouzis I, Varonos D, Cokkinos D, Tsakiris S (2005) Changes in antioxidant status, protein concentration, acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase activities in the brain of hyper- and hypothyroid adult rats. Metab Brain Dis 20:129–139

    Article  PubMed  CAS  Google Scholar 

  • Cermak JM, Holler T, Jackson DA, Blusztajn JK (1998) Prenatal availability of choline modifies development of the hippocampal cholinergic system. FASEB J 12:349–357

    PubMed  CAS  Google Scholar 

  • Cohen EL, Wurtman RJ (1976) Brain acetylcholine: control by dietary choline. Science 191:561–562

    Article  PubMed  CAS  Google Scholar 

  • Committee on Care and Use of Laboratory Animals (1985) Guide for the care and use of laboratory animals. Institute of Laboratory Animal Resources, National Research Council, Washington, DC, p 83

    Google Scholar 

  • Conford EM, Braun LD, Oldendorf WH (1978) Carrier mediated blood–brain barrier transport of choline and certain choline analogs. J Neurochem 30:299−308

    Article  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  • Fisher MC, Zeisel SH, Mar MH, Sadler TW (2001) Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos. Teratology 64:114–122

    Article  PubMed  CAS  Google Scholar 

  • Guyton AC, Hall JE (2000) Transport of substances through the cell membrane. In: Textbook of medical physiology, (10th edn). WB Saunders Company, Philadelphia, pp 40–51

  • Hernandez J (1987) Brain Na+,K+-ATPase activity possibly regulated by a specific serotonin receptor. Brain Res 408:399–402

    Article  PubMed  CAS  Google Scholar 

  • Kilbinger H, Kruel MR (1981) Choline inhibits acetylcholine release via presynaptic muscarinic receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 316:131–134

    Article  CAS  Google Scholar 

  • Klegeris A, Korkina LG, Greenfield SA (1995) A possible interaction between acetylcholinesterase and dopamine molecules during autoxidation of the amine. Free Radic Biol Med 18:223–230

    Article  PubMed  CAS  Google Scholar 

  • Kouniniotou-Krontiri P, Tsakiris S (1989) Time dependence of Li+ action on acetylcholinesterase activity in correlation with spontaneous quantal release of acetylcholine in rat diaphragm. Jpn J Physiol 39:429–440

    Article  PubMed  CAS  Google Scholar 

  • Lees GJ, Lehmann A, Sandberg M, Hamberger A (1990) The neurotoxicity of ouabain, a sodium–potassium ATPase inhibitor, in the rat hippocampus. Neurosci Lett 120:159–162

    Article  PubMed  CAS  Google Scholar 

  • Liapi C, Feskou I, Zarros A, Galanopoulou P, Tsakiris S (2007) Effects of gestational and lactational choline deprivation on brain antioxidant status, acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase activities in offspring rats. Clin Chem Lab Med 45:651–656

    Article  PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Mata M, Fink DJ, Gainer H, Smith CB, Davidsen L, Savakis H, Schwartz WJ, Sokoloff L (1980) Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. J Neurochem 34:213–215

    Article  PubMed  CAS  Google Scholar 

  • Meck WH, Williams CL (2003) Metabolic imprinting of choline by its availability during gestation: implications for memory and attentional processing across the lifespan. Neurosci Biobehav Rev 27:385–399

    Article  PubMed  CAS  Google Scholar 

  • Molloy AM, Mills JL, Cox C, Daly SF, Conley M, Brody LC, Kirke PN, Scott JM, Ueland PM (2005) Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery. Am J Clin Nutr 82:836–842

    PubMed  CAS  Google Scholar 

  • Montoya D, Swartzwelder HS (2000) Prenatal choline supplementation alters hippocampal N-methyl-d-aspartate receptor-mediated neurotransmission in adult rats. Neurosci Lett 296:85–88

    Article  PubMed  CAS  Google Scholar 

  • Sanui H, Rubin H (1982) The role of magnesium in cell proliferation and transformation. In: Boynton AL, McKochan WL, Whitfield JP (eds) Ions, cell proliferation and cancer. Academic, New York, pp 517–537

    Google Scholar 

  • Sastry BS, Phillis JW (1977) Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+,K+-ATPase inhibitors. Can J Physiol Pharmacol 55:170–180

    Article  PubMed  CAS  Google Scholar 

  • Schulpis KH, Giannoulia-Karantana A, Papaconstantinou ED, Parthimos T, Tjamouranis I, Tsakiris S (2006a) Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C–>T genotype and moderate hyperhomocysteinaemia. The role of l-phenylalanine and l-alanine. Clin Chem Lab Med 44:423–427

    Article  PubMed  CAS  Google Scholar 

  • Schulpis KH, Kalimeris K, Bakogiannis C, Tsakiris T, Tsakiris S (2006b) The effect of in vitro homocystinuria on the suckling rat hippocampal acetylcholinesterase. Metab Brain Dis 21:21–28

    Article  PubMed  CAS  Google Scholar 

  • Streck EL, Zugno AI, Tagliari B, Sarkis JJF, Wajner M, Wannmacher CMD, Wyse ATS (2002a) On the mechanism of the inhibition of Na+,K+-ATPase activity caused by homocysteine. Int J Dev Neurosci 20:77–81

    Article  PubMed  CAS  Google Scholar 

  • Streck EL, Zugno AI, Tagliari B, Wannmacher CMD, Wajner M, Wyse ATS (2002b) Inhibition of Na+,K+-ATPase activity by the metabolites accumulating in homocystinuria. Metab Brain Dis 17:83–91

    Article  PubMed  CAS  Google Scholar 

  • Swann AC (1984) (Na+,K+)-adenosine triphosphatase regulation by the sympathetic nervous system: effects of noradrenergic stimulation and lesion in vivo. J Pharmacol Exp Ther 228:304–311

    PubMed  CAS  Google Scholar 

  • Tsakiris S (2001) Effects of l-phenylalanine on acetylcholinesterase and Na+,K+-ATPase activities in adult and aged rat brain. Mech Ageing Dev 122:491–501

    Article  PubMed  CAS  Google Scholar 

  • Tsakiris S, Angelogianni P, Schulpis KH, Behrakis P (2000) Protective effect of l-cysteine and glutathione on rat brain Na+,K+-ATPase inhibition induced by free radicals. Z Naturforsch [C] 55:271–277

    CAS  Google Scholar 

  • Tucek S (1993) Short-term control of the synthesis of acetylcholine. Prog Biophys Mol Biol 60:59–69

    Article  PubMed  CAS  Google Scholar 

  • Zeisel SH (2004) Nutritional importance of choline for brain development. J Am Coll Nutr 23:621s–626s

    PubMed  CAS  Google Scholar 

  • Zeisel SH (2005) Choline, homocysteine, and pregnancy. Am J Clin Nutr 82:719–720

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the University of Athens and funded by the University of Athens Special Account for Research Funding (no.70/4/6562). No conflict of interest exists. The authors wish to acknowledge their appreciation to the medical students Elena Gkrouzman and Zois Mellios for their significant assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stylianos Tsakiris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liapi, C., Feskou, I., Zarros, A. et al. Equilibrated diet restores the effects of early age choline-deficient feeding on rat brain antioxidant status and enzyme activities: the role of homocysteine, l-phenylalanine and l-alanine. Metab Brain Dis 23, 289–301 (2008). https://doi.org/10.1007/s11011-008-9097-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-008-9097-2

Keywords

Navigation