Advertisement

Neurophysiology

, Volume 44, Issue 1, pp 14–19 | Cite as

Aging- and Experimental Mitochondrial Dysfunction-Related Modifications of Energy Metabolism in Brainstem Neurons

  • E. É. Kolesnikova
  • V. I. Nosar’
  • I. N. Man’kovskaya
  • T. V. Serebrovskaya
Article

Using a polarographic technique, we studied the peculiarities of energy metabolism in neurons of the rat brainstem structures related to normal physiological aging. Experiments were carried out under in vitro conditions on mitochondrial (MCh) suspensions prepared from the brainstem cells of young and old rats. In addition, we examined, using the same technique, the parameters of oxidative phosphorylation in analogous MCh suspension under conditions of experimental MCh dysfunction induced by single systemic injection of rotenone into young animals. In the case where we used a succinate + rotenone mixture as the substrate for oxidation, the intensity of ADP-stimulated respiration (V3) in preparations from brainstem neurons of old animals was significantly smaller (against the background of a decrease in the efficacy of respiration control, V3/V4). If a mixture glutamate + malate was used as the substrate for oxidation, the V3 and the efficacy of phosphorylation (ADP/O) decreased significantly. The experimental MCh dysfunction resulted in the lowering of practically all parameters of oxidation and phosphorylation under conditions of oxidation of glutamate + malate, as well as V3, V3/V4, and ADP/O, in the case where we used succinate + rotenone as the substrate for oxidation. Less expressed changes in the recorded indices upon oxidation of succinate + rotenone were indicative of activation of the succinate oxidase pathway; this preserved the electrotransport function of the respiratory chain in the MCh on a certain level and the ability of the latter to provide oxidative phosphorylation.

Keywords

brainstem medulla mitochondrial function oxidative phosphorylation polarography aging rotenone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Y. H. Wei, Y. S. Ma, H. C. Lee, et al., “Mitochondrial theory of aging matures – roles of mtDNA mutation and oxidative stress in human aging,” Zhonghua Yi Xue Za Zhi (Taipei), 64, 259–70 (2001).Google Scholar
  2. 2.
    H. C. Lee and Y. H. Wei, “Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging,” Exp. Biol. Med., 232, No. 5, 592–606 (2007).Google Scholar
  3. 3.
    L. D. Luk’yanova, “Bioenergetic hypoxia: idea, mechanisms, and techniques for correction,” Byul. Éksp. Biol. Med., 124, 244–254 (1997).Google Scholar
  4. 4.
    L. D. Luk’yanova, “Pharmacology of mitochondrial dysfunction,” Consil. Med., 9, 102–103 (2007).Google Scholar
  5. 5.
    A. L. Bianchi, M. Denavit-Saubie, and J. Champagnat, “Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters,” Physiol. Rev., 75, 1–45 (1995).PubMedGoogle Scholar
  6. 6.
    J. D. Wood, W. J. Watson, and A. J. Ducker, “The effect of hypoxia on brain gamma-aminobutyric acid levels,” J. Neurochem., 15, 603–608 (1968).PubMedCrossRefGoogle Scholar
  7. 7.
    J. E. Madl and S. M. Royer, “Glutamate dependence of GABA levels in neurons of hypoxic and hypoglycemic rat hippocampal slices,” Neuroscience, 96, 657–664 (1999).CrossRefGoogle Scholar
  8. 8.
    J. Bove, D. Prou, C. Perier, and S. Przedborski, “Toxininduced models of Parkinson’s disease,” NeuroRx, 2, 484–494 (2005).PubMedCrossRefGoogle Scholar
  9. 9.
    D. J. Talpade, J. G. Green, D. S. Higgins, Jr, and J. T. Greenamyre, “In vivo labeling of mitochondrial complex I (NADH:ubiquinone oxidoreductase) in rat brain using [(3)H]dihydrorotenone,” J. Neurochem., 75, 2611–2621 (2000).PubMedCrossRefGoogle Scholar
  10. 10.
    A. L. Ton’shin, N. V. Lobisheva, L. S. Yaguzhiskii, et al., “Effect of inhibitory neuromediator glycine on slow destructive processes in cerebral slices in anoxia,” Biokhimiya, 72, 631–641 (2007).Google Scholar
  11. 11.
    B. Chance and G. Williams, “The respiratory chain and oxidative phosphorylation,” Adv. Enzymol., 17, 65–134 (1956).Google Scholar
  12. 12.
    R. W. Estabrook, “Mitochondrial respiratory control and the polarographic measurement of ADP:O Ratio,” Methods Enzymol., 10, 41–47 (1967).CrossRefGoogle Scholar
  13. 13.
    T. B. Sherer, J.-H. Kim, R. Betarbet, and J. T. Greenamyre, “Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and α-synuclein aggregation,” Exp. Neurol., 179, 9–16 (2003).PubMedCrossRefGoogle Scholar
  14. 14.
    E. Angelie, A. Bonmartin, A. Boudraa, et al., “Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study,” Am. J. Neuroradiol., 22, 119–127 (2001).PubMedGoogle Scholar
  15. 15.
    B. Draganski, J. Ashburner, C. Hutton, et al., “Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ),” Neuroimage, 55, 1423–1434 (2011).PubMedCrossRefGoogle Scholar
  16. 16.
    A. D. Beavis, “Upper and lower limits of the charge translocation stoichiometry of mitochondrial electron transport,” J. Biol. Chem., 262, 6165–6173 (1987).PubMedGoogle Scholar
  17. 17.
    M. D. Moser, S. Matsuzaki, and K. M. Humphries, “Inhibition of succinate-linked respiration and complex II activity by hydrogen peroxide,” Arch. Biochem. Biophys., 488, 69–75 (2009).PubMedCrossRefGoogle Scholar
  18. 18.
    F. Boumezbeur, G. F. Mason, R. A. de Graaf, et al., “Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy,” J. Cerebr. Blood Flow Metab., 30, 211–221 (2010).CrossRefGoogle Scholar
  19. 19.
    D. H. Salat, R. L. Buckner , A. Z. Snyder, et al., “Thinning of the cerebral cortex in aging,” Cerebr. Cortex, 14, 21–730 (2004).CrossRefGoogle Scholar
  20. 20.
    G. Kalpouzos, G. Chetelat, J. C. Baron, et al., “Voxelbased mapping of brain gray matter volume and glucose metabolism profiles in normal aging,” Neurobiol. Aging, 30, 112–124 (2009).PubMedCrossRefGoogle Scholar
  21. 21.
    P. C. Tumeh, A. Alavi, M. Houseni, et al., “Structural and functional imaging correlates for age-related changes in the brain,” Semin. Nucl. Med., 37, 69–87 (2007).PubMedCrossRefGoogle Scholar
  22. 22.
    E. V. Sullivan and A. Pfefferbaum, “Neuroradiological characterization of normal adult ageing,” Br. J. Radiol., 80, S99–S108 (2007).PubMedCrossRefGoogle Scholar
  23. 23.
    X. Wang, A. Zaidi, R. Pal, et al., “Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress,” BMC Neurosci., 10 (2009).Google Scholar
  24. 24.
    R. Betarbet, T. B. Sherer, G. MacKenzie, et al., “Chronic systemic pesticide exposure reproduces feature of Parkinson’s disease,” Nat. Neurosci., 3, 1301–1306 (2000).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2012

Authors and Affiliations

  • E. É. Kolesnikova
    • 1
  • V. I. Nosar’
    • 1
  • I. N. Man’kovskaya
    • 1
  • T. V. Serebrovskaya
    • 1
  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKyivUkraine

Personalised recommendations