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Manganese Alters Rat Brain Amino Acids Levels

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Abstract

Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein, and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism. In the present study, we analyzed whole rat brain amino acid content subsequent to four or eight intraperitoneal injections, with 25 mg MnCl2/kg/day, at 48-h intervals. We noted a significant increase in glycine brain levels after four or eight Mn injections (p < 0.05 and p < 0.01, respectively) and arginine also after four or eight injections (p < 0.001). Significant increases were also noted in brain proline (p < 0.01), cysteine (p < 0.05), phenylalanine (p < 0.01), and tyrosine (p < 0.01) levels after eight Mn injections vs. the control group. These findings suggest that Mn-induced alterations in amino acid levels secondary to Mn affect the neurochemical milieu.

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References

  1. Aschner J, Aschner M (2005) Nutritional aspects of Mn homeostasis. Mol Asp Med 26:353–362

    Article  CAS  Google Scholar 

  2. Erikson KM, Syversen T, Aschner JL, Aschner M (2005) Interactions between excessive manganese exposures and dietary iron-deficiency in neurodegeneration. Environ Toxicol Pharmacol 19:415–421

    Article  PubMed  CAS  Google Scholar 

  3. Aschner M, Guilarte TR, Schneider JS, Zheng W (2007) Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol 221:131–147

    Article  PubMed  CAS  Google Scholar 

  4. Golub MS, Hogrefe CE, Germann SL, Tran TT, Beard JL et al (2005) Neurobehavioral evaluation of rhesus monkey infants fed cow’s milk formula, soy formula, or soy formula with added manganese. Neurotoxicol Teratol 27:615–627

    Article  PubMed  CAS  Google Scholar 

  5. Erikson KM, Thompson K, Aschner J, Aschner M (2007) Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther 113:369–377

    Article  PubMed  CAS  Google Scholar 

  6. Aschner M, Erikson KM, Herrero Hernandez E, Tjalkens R (2009) Manganese and its role in Parkinson’s disease: from transport to neuropathology. Neuromol Med 11:252–266

    Article  CAS  Google Scholar 

  7. Bagga P, Patel AB (2012) Regional cerebral metabolism in mouse under chronic manganese exposure: implications for manganism. Neurochem Int 60:177–185

    Article  PubMed  CAS  Google Scholar 

  8. Fitsanakis VA, Au C, Erikson KM, Aschner M (2006) The effects of manganese on glutamate, dopamine and gamma-aminobutyric acid regulation. Neurochem Int 48:426–433

    Article  PubMed  CAS  Google Scholar 

  9. Erikson KM, Shihabi ZK, Aschner JL, Aschner M (2002) Manganese accumulates in iron-deficient rat brain regions in a heterogeneous fashion and is associated with neurochemical alterations. Biol Trace Elem Res 87:143–156

    Article  PubMed  CAS  Google Scholar 

  10. Stanwood GD, Leitch DB, Savchenko V, Wu J, Fitsanakis VA et al (2009) Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia. J Neurochem 110:378–389

    Article  PubMed  CAS  Google Scholar 

  11. Zwingmann C, Leibfritz D, Hazell AS (2004) Brain energy metabolism in a sub-acute rat model of manganese neurotoxicity: an ex vivo nuclear magnetic resonance study using [1-13C]glucose. Neurotoxicology 25:573–587

    Article  PubMed  CAS  Google Scholar 

  12. Koning T, Fuchs S, Klomp L (2007) Serine, glycine and threonine. In: Lajtha A (ed) Handbook of neurochemistry and molecular neurobiology: amino acids and peptides in the nervous system. Springer Science, New York, pp 25–41

    Google Scholar 

  13. Snyder SH, Logan WJ, Bennett JP, Arregui A (1973) Amino acids as central nervous transmitters: biochemical studies. Neurosci Res (N Y) 5:131–157

    CAS  Google Scholar 

  14. Bennett JP Jr, Logan WJ, Snyder SH (1973) Amino acids as central nervous transmitters: the influence of ions, amino acid analogues, and ontogeny on transport systems for L-glutamic and L-aspartic acids and glycine into central nervous synaptosomes of the rat. J Neurochem 21:1533–1550

    Article  PubMed  CAS  Google Scholar 

  15. Boehning D, Snyder SH (2003) Novel neural modulators. Annu Rev Neurosci 26:105–131

    Article  PubMed  CAS  Google Scholar 

  16. Baranano DE, Ferris CD, Snyder SH (2001) Atypical neural messengers. Trends Neurosci 24:99–106

    Article  PubMed  CAS  Google Scholar 

  17. Swanson T, Kim S, Glucksman M (2010) Biochemistry, molecular biology & genetics. Wolters Kluwer–Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  18. Hietanen E, Kilpio J, Savolainen H (1981) Neurochemical and biotransformational enzyme responses to manganese exposure in rats. Arch Environ Contam Toxicol 10:339–345

    Article  PubMed  CAS  Google Scholar 

  19. Zheng W, Ren S, Graziano JH (1998) Manganese inhibits mitochondrial aconitase: a mechanism of manganese neurotoxicity. Brain Res 799:334–342

    Article  PubMed  CAS  Google Scholar 

  20. Zwingmann C, Leibfritz D, Hazell AS (2003) Energy metabolism in astrocytes and neurons treated with manganese: relation among cell-specific energy failure, glucose metabolism, and intercellular trafficking using multinuclear NMR-spectroscopic analysis. J Cereb Blood Flow Metab 23:756–771

    Article  PubMed  CAS  Google Scholar 

  21. Silva AC, Bock NA (2008) Manganese-enhanced MRI: an exceptional tool in translational neuroimaging. Schizophr Bull 34:595–604

    Article  PubMed  Google Scholar 

  22. Cohen SA, Michaud DP (1993) Synthesis of a fluorescent derivatizing reagent, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, and its application for the analysis of hydrolysate amino acids via high-performance liquid chromatography. Anal Biochem 211:279–287

    Article  PubMed  CAS  Google Scholar 

  23. Erikson KM, Dobson AW, Dorman DC, Aschner M (2004) Manganese exposure and induced oxidative stress in the rat brain. Sci Total Environ 334–335:409–416

    Article  PubMed  Google Scholar 

  24. Bonilla E, Arrieta A, Castro F, Davila JO, Quiroz I (1994) Manganese toxicity: free amino acids in the striatum and olfactory bulb of the mouse. Invest Clin 35:175–181

    PubMed  CAS  Google Scholar 

  25. Lipe GW, Duhart H, Newport GD, Slikker W Jr, Ali SF (1999) Effect of manganese on the concentration of amino acids in different regions of the rat brain. J Environ Sci Health B 34:119–132

    Article  PubMed  CAS  Google Scholar 

  26. Yokel RA (2006) Blood–brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis 10:223–253

    PubMed  Google Scholar 

  27. Chandra SV, Malhotra KM, Shukla GS (1982) GABAergic neurochemistry in manganese exposed rats. Acta Pharmacol Toxicol (Copenh) 51:456–458

    Article  CAS  Google Scholar 

  28. Lai JC, Leung TK, Lim L (1984) Differences in the neurotoxic effects of manganese during development and aging: some observations on brain regional neurotransmitter and non-neurotransmitter metabolism in a developmental rat model of chronic manganese encephalopathy. Neurotoxicology 5:37–47

    PubMed  CAS  Google Scholar 

  29. Huang J, Philbert MA (1996) Cellular responses of cultured cerebellar astrocytes to ethacrynic acid-induced perturbation of subcellular glutathione homeostasis. Brain Res 711:184–192

    Article  PubMed  CAS  Google Scholar 

  30. Lyons J, Rauh-Pfeiffer A, Yu YM, Lu XM, Zurakowski D et al (2000) Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet. Proc Natl Acad Sci U S A 97:5071–5076

    Article  PubMed  CAS  Google Scholar 

  31. Takeda A, Sotogaku N, Oku N (2003) Influence of manganese on the release of neurotransmitters in rat striatum. Brain Res 965:279–282

    Article  PubMed  CAS  Google Scholar 

  32. Santos D, Milatovic D, Andrade V, Batoreu MC, Aschner M et al (2012) The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain. Toxicology 292:90–98

    Article  PubMed  CAS  Google Scholar 

  33. Altindag ZZ, Baydar T, Engin AB, Sahin G (2003) Effects of the metals on dihydropteridine reductase activity. Toxicol In Vitro 17:533–537

    Article  PubMed  CAS  Google Scholar 

  34. Kaufman S (1993) New tetrahydrobiopterin-dependent systems. Annu Rev Nutr 13:261–286

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by FCT (Foundation for Science and Technology of Portugal; SFRH/BD/64128/2009), by i-Med.UL, Faculty of Pharmacy, University of Lisbon and a grant from the National Institute of Environmental Health Sciences ES R01 10563 (MA).

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Authors and Affiliations

  1. I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Dinamene Santos, M. Camila Batoreu & A. P. Marreilha dos Santos

  2. I-Med.UL, Department of Biochemistry, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Isabel Almeida & Ruben Ramos

  3. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Michael Aschner

  4. Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

    M. Sidoryk-Wegrzynowicz

Authors
  1. Dinamene Santos
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  2. M. Camila Batoreu
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  3. Isabel Almeida
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  4. Ruben Ramos
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  5. M. Sidoryk-Wegrzynowicz
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  6. Michael Aschner
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  7. A. P. Marreilha dos Santos
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Correspondence to A. P. Marreilha dos Santos.

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Santos, D., Batoreu, M.C., Almeida, I. et al. Manganese Alters Rat Brain Amino Acids Levels. Biol Trace Elem Res 150, 337–341 (2012). https://doi.org/10.1007/s12011-012-9504-8

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  • DOI: https://doi.org/10.1007/s12011-012-9504-8

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