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In Vitro Metabolomic Approach to Hippocampal Neurodegeneration Induced by Trimethyltin

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Abstract

Search for indicators of neurodegenerative disorders is a hot topic where much research remains to be done. Our aim was to determine proton nuclear magnetic resonance (1H-NMR) spectra of brain metabolites in the trimethyltin (TMT) model of neurodegeneration. Male Wistar rats were subjected to TMT or saline and were sacrificed on day 3 or 24 after administration. 1H-NMR spectrum was measured on the 600 MHz Varian VNMRS spectrometer in nano-probe in the volume of 40 μl of hippocampal extracts. TMT administration resulted in reduction of the hippocampal weight on day 24. Of the sixteen identified metabolite spectra, decreased aspartate and increased glutamine contents were observed in the initial asymptomatic stage of neurodegeneration on day 3 in hippocampal extracts of TMT exposed rats compared to sham animals. Increased myo-inositol content was observed on day 24. The presented data provide further knowledge about this experimental model and putative indicators of neuronal damage.

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References

  1. Neha Sodhi RK, Jaggi AS, Singh N (2014) Animal models of dementia and cognitive dysfunction. Life Sci 109:73–86. doi:10.1016/j.lfs.2014.05.017

    Article  CAS  PubMed  Google Scholar 

  2. Koczyk D (1996) How does trimethylthin affect the brain: facts and hypotheses. Acta Neurobiol Exp 56:587–596

    CAS  Google Scholar 

  3. Geloso MC, Corvino V, Michetti F (2011) Trimethyltin-induced hippocampal degeneration as a tool to investigate neurodegenerative processes. Neurochem Int 58:729–738. doi:10.1016/j.neuint.2011.03.009

    Article  CAS  PubMed  Google Scholar 

  4. Gasparova Z, Janega P, Stara V, Ujhazy E (2012) Early and late stage of neurodegeneration induced by trimethyltin in hippocampus and cortex of male Wistar rats. Neuro Endocrinol Lett 33:689–696

    CAS  PubMed  Google Scholar 

  5. Ross BD, Bluml S, Cowan R, Danielsen E, Farrow N, Gruetter R (1997) In vivo magnetic resonance spectroscopy of human brain: the biophysical basis of dementia. Biophys Chem 68:161–172. doi:10.1016/s0301-4622(97)00032-x

    Article  CAS  PubMed  Google Scholar 

  6. Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed 13:129–153. doi:10.1002/1099-1492(200005)13:3<129::aid-nbm619>3.3.co;2-m

    Article  CAS  PubMed  Google Scholar 

  7. Shin EJ, Suh SK, Lim YK, Jhoo WK, Hjelle OP, Ottersen OP, Shin CY, Ko KH, Kim WK, Kim DS, Chun W, Ali S, Kim HC (2005) Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis. Neuroscience 133:715–727. doi:10.1016/j.neuroscience.2005.02.030

    Article  CAS  PubMed  Google Scholar 

  8. McPherson CA, Merrick BA, Harry GJ (2014) In vivo molecular markers for pro-inflammatory cytokine M1 stage and resident microglia in trimethyltin-induced hippocampal injury. Neurotox Res 25:45–56. doi:10.1007/s12640-013-9422-3

    Article  CAS  PubMed  Google Scholar 

  9. Figiel I, Dzwonek K (2007) TNFα and TNF receptor 1 expression in the mixed neuronal-glia cultures of hippocampal dentate gyrus exposed to glutamate or trimethyltin. Brain Res 1131:17–28. doi:10.1016/j.brainres.2006.10.095

    Article  CAS  PubMed  Google Scholar 

  10. Brock TO, O’Callaghan JP (1987) Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. J Neurosci 4:931–942

    Google Scholar 

  11. Whittington DL, Woodruff ML, Baisden RH (1989) The time-course of trimethyltin-induced fiber and terminal degeneration in hippocampus. Neurotoxicol Teratol 11:21–33. doi:10.1016/0892-0362(89)90081-0

    Article  CAS  PubMed  Google Scholar 

  12. Macri MA, D’Alessandro N, Di Giulio C, Di Iorio P, Di Luzio S, Giuliani P, Bianchi G, Esposito E (2006) Regional changes in metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: a quantitative proton MRS study. Neurobiol Aging 27:98–104. doi:10.1016/j.neurobiolaging.2005.01.007

    Article  CAS  PubMed  Google Scholar 

  13. Gasparova Z, Stara V, Janega P, Navarova J, Sedlackova N, Mach M, Ujhazy E (2014) Pyridoindole antioxidant-induced preservation of rat hippocampal pyramidal cell number linked with reduction of oxidative stress yet without influence on cognitive deterioration in Alzheimer-like neurodegeneration. Neuro Endocrinol Lett 35:454–462

    PubMed  Google Scholar 

  14. Bobinski M, Wegiel J, Wisniewski HM, Tarnawski M, Bobinski M, Reisberg B, De Leon MJ, Miller DC (1996) Neurofibrillary pathology—correlation with hippocampal formation atrophy in Alzheimer disease. Neurobiol Aging 17:909–919. doi:10.1016/s0197-4580(96)00160-1

    CAS  PubMed  Google Scholar 

  15. Double K, Halliday G, Kril J, Harasty J, Cullen K, Brooks W, Creasey H, Broe G (1996) Topography of brain atrophy during normal aging and Alzheimer’s disease. Neurobiol Aging 17:513–521. doi:10.1016/s0197-4580(96)00005-x

    Article  CAS  PubMed  Google Scholar 

  16. Kril JJ, Patel S, Harding AJ, Halliday GM (2002) Neuron loss from the hippocampus of Alzheimer’s disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol 103:370–376. doi:10.1007/s00401-001-0477-5

    Article  PubMed  Google Scholar 

  17. Kril JJ, Hodges J, Halliday G (2004) Relationship between hippocampal volume and CA1 neuron loss in brains of humans with and without Alzheimer’s disease. Neurosci Lett 361:9–12. doi:10.1016/j.neulet.2004.02.001

    Article  CAS  PubMed  Google Scholar 

  18. Simic G, Kostovic I, Winblad B, Bogdanovic N (1997) Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer’s disease. J Comp Neurol 379:482–494. doi:10.1002/(sici)1096-9861(19970324)379:4<482::aid-cne2>3.0.co;2-z

    Article  CAS  PubMed  Google Scholar 

  19. West MJ, Coleman PD, Flood DG, Troncoso JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 344:769–772. doi:10.1016/S0140-6736(94)92338-8

    Article  CAS  PubMed  Google Scholar 

  20. D’Aniello S, Somorjai I, Garcia-Fernàndez J, Topo E, D’Aniello A (2011) d-Aspartic acid is a novel endogenous neurotransmitter. FASEB J 25:1014–1027. doi:10.1096/fj.10-168492

    Article  PubMed  Google Scholar 

  21. Errico F, Nisticò R, Palma G, Federici M, Affuso A, Brilli E, Topo E, Centonze D, Bernardi G, Bozzi Y, D’Aniello A, Di Lauro R, Mercuri NB, Usiello A (2008) Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci 37:236–246. doi:10.1016/j.mcn.2007.09.012

    Article  CAS  PubMed  Google Scholar 

  22. Errico F, Nistico R, Napoletano F, Mazzola C, Astone D, Pisapia T, Giustizieri M, D’Aniello A, Mercuri NB, Usiello A (2011) Increased d-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging 32:2229–2243. doi:10.1016/j.neurobiolaging.2010.01.002

    Article  CAS  PubMed  Google Scholar 

  23. Topo E, Soricelli A, Di Maio A, D’Aniello E, Di Fiore MM, D’Aniello A (2010) Evidence for the involvement of d-aspartic acid in learning and memory of rat. Amino Acids 38:1561–1569. doi:10.1007/s00726-009-0369-x

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Zhang J (2000) Recent development in NMDA receptors. Chin Med J (Engl) 10:948–956

    Google Scholar 

  25. Petrović M, Horák M, Sedláček M, Vyklický L Jr (2005) Physiology and pathology of NMDA receptors. Prague Med Rep 106:113–136

    PubMed  Google Scholar 

  26. Walton HS, Dodd PR (2007) Glutamate–glutamine cycling in Alzheimer’s disease. Neurochem Int 50:1052–1066. doi:10.1016/j.neuint.2006.10.007

    Article  CAS  PubMed  Google Scholar 

  27. Haris M, Cai K, Singh A, Hariharan H, Reddy R (2011) In vivo mapping of brain myo-inositol. Neuroimage 54:2079–2085. doi:10.1016/j.neuroimage.2010.10.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lin Y, Yao J, Chen Y, Pang L, Li H, Cao Z, You K, Dai H, Wu R (2014) Hippocampal neurochemical changes in senescent mice induced with chronic injection of d-galactose and NaNO2: an in vitro high-resolution NMR spectroscopy study at 9.4 T. PLoS One 9(2):e88562. doi:10.1371/journal.pone.0088562

    Article  PubMed  PubMed Central  Google Scholar 

  29. Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD (1993) Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 187:433–437. doi:10.1148/radiology.187.2.8475286

    Article  CAS  PubMed  Google Scholar 

  30. Huang W, Alexander GE, Chang L, Shetty HU, Krasuski JS, Rapoport SI, Schapiro MB (2001) Brain metabolite concentration and dementia severity in Alzheimer’s disease: a 1H-MRS study. Neurology 57:626–632. doi:10.1212/wnl.57.4.626

    Article  CAS  PubMed  Google Scholar 

  31. Pfefferbaum A, Adalsteinsson A, Spielman D, Sullivan EV, Lim KO (1999) In vivo brain concentrations of N-acetyl compounds, creatinine and chlorine in Alzheimer’s disease. Arch Gen Psychiatry 56:185–192. doi:10.1001/archpsyc.56.2.185

    Article  CAS  PubMed  Google Scholar 

  32. Adalsteinsson E, Sullivan EV, Kleinhans N, Spielman DM, Pfefferbaum A (2000) Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer’s disease. Lancet 355:1696–1697. doi:10.1016/S0140-6736(00)02246-7

    Article  CAS  PubMed  Google Scholar 

  33. Reyngoudt H, Claeys T, Vlerick L, Verleden S, Acou M, Deblaere K, De Deene Y, Audenaert K, Goethals I, Achten E (2012) Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal aging brain: a (1)H-MRS study. Eur J Radiol 81:223–231. doi:10.1016/j.ejrad.2011.01.106

    Article  Google Scholar 

  34. Zhang X, Liu H, Wu J, Zhang X, Liu M, Wang Y (2009) Metabonomic alterations in hippocampus, temporal and prefrontal cortex with age in rats. Neurochem Int 54:481–487. doi:10.1016/j.neuint.2009.02.004

    Article  PubMed  Google Scholar 

  35. Paban V, Fauvelle F, Alescio-Lautier B (2010) Age-related changes in metabolic profiles of rat hippocampus and cortices. Eur J Neurosci 31:1063–1073. doi:10.1111/j.1460-9568.2010.07126.x

    Article  PubMed  Google Scholar 

  36. Gasparova Z, Janega P, Pronayova N, Liptaj T (2012) Middle-aged rat hippocampus and some early changes accompanying aging. Cent Eur J Biol 7:810–816. doi:10.2478/s11535-012-0074-8

    Google Scholar 

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Acknowledgments

The study was supported by the Slovak Grant Agency for Science VEGA 2/0054/15. The authors thank to Mrs. Julia Polakova for her technical assistance.

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Authors and Affiliations

  1. Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia

    Zdenka Gasparova & Veronika Stara

  2. Department of NMR and Mass Spectroscopy, Faculty of Food and Chemical Technology, Slovak University of Technology, Bratislava, Slovakia

    Nada Pronayova & Tibor Liptaj

  3. Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

    Veronika Stara

Authors
  1. Zdenka Gasparova
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  2. Nada Pronayova
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  3. Veronika Stara
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Correspondence to Zdenka Gasparova.

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The authors declare that there are no conflicts of interest.

Ethical Approval

All procedures involving animals were performed in compliance with the Principles of Laboratory Animal Care issued by the Ethical Committee of the Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences of Slovakia and by the State Veterinary and Food Administration of Slovakia. The welfare of animals used for research was respected.

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Gasparova, Z., Pronayova, N., Stara, V. et al. In Vitro Metabolomic Approach to Hippocampal Neurodegeneration Induced by Trimethyltin. Neurochem Res 41, 715–721 (2016). https://doi.org/10.1007/s11064-015-1740-9

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  • DOI: https://doi.org/10.1007/s11064-015-1740-9

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