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Intermittent Hypoxia and Experimental Parkinson’s Disease

  • Maria V. Belikova
  • Evgenia E. KolesnikovaEmail author
  • Tatiana V. Serebrovskaya
Chapter

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease which is characterized by a progressive degeneration of dopaminergic neurons in the midbrain. A most reliable mechanism causing the apoptosis in dopaminergic structures of the brain during aging and Parkinson’s disease is the activation of oxidative stress. Until now, effective means for the prevention of dopaminergic neurons degeneration and for the retention of damaged neurons functioning is still lacking. A promising way to slacken the pace of degenerative processes during aging and PD could be the adaptation to intermittent hypoxia. Such adaptation strengthens dopamine (DA) synthesis and release at peripheral chemoreceptors in carotid bodies and activates tyrosine hydroxylase – a rate-limiting enzyme for catecholamine synthesis. In this chapter, we examined three groups of rats: adult, old, and old rats with experimental DA deficiency. It was revealed that there was an asymmetry of dopamine distribution between the right and left striatum of adult rats. Prevalent quantity of dopamine was concentrated in right hemisphere. During aging DA, production decreased in the examined structures mainly in right hemisphere of the striatum, so its distribution asymmetry diminished. In PD animals, this decrease was much more expressed and led to practically total abolishment of quantitative difference between right and left hemispheres. Two-week course of intermittent hypoxia training (IHT, five cycles of 15-min exposures to 12% O2 followed by 15-min room air breathing per day) increased dopamine synthesis in old and experimental PD animals, especially in the right striatum, restored partially the asymmetry of DA distribution between brain hemispheres. IHT also decreased the intensity of lipid peroxidation. Increased plasma antioxidant activity positively correlated with increased DA concentration in the striatum. Therefore, IHT could serve as a good perspective means for the deceleration of aging and prevention/treatment of Parkinson’s disease.

Keywords

Substantia Nigra Left Hemisphere Carotid Body Intermittent Hypoxia Glomus Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

6-OHDA

6-hydroxydopamine

CAT

Catalase

CB

Carotid bodies

DA

Dopamine

EDAD

Experimental DA deficiency

GFAP

Glial fibrillary acid protein

HIF

Hypoxia inducible factor

IHT

Intermittent hypoxia training

MAO

Monoamine oxidase

MDA

Malondialdehyde

PD

Parkinson’s disease

ROS

Reactive oxygen species

SN

Substantia nigra

SOD

Superoxide dismutase

TH

Tyrosine hydroxylase

References

  1. 1.
    Wei YH, Ma YS, Lee HC, et al. Mitochondrial theory of aging matures-roles of mtDNA mutation and oxidative stress in human aging. Zhonghua Yi Xue Za Zhi (Taipei). 2001;64:259–70.Google Scholar
  2. 2.
    Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med. 2007;232:592–606.Google Scholar
  3. 3.
    Orr WC, Sohal RS. Effects of Cu, Zn superoxide dismutase overexpression on life span and resistance to oxidative stress in transgenic drosophila melanogaster. Arch Biochem Biophys. 1993;301:34–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Kish SJ, Shannak K, Rajput A, et al. Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson’s disease. J Neurochem. 1992;58:642–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Foster ER, Black KJ, Antenor-Dorsey JA, et al. Motor asymmetry and substantia nigra volume are related to spatial delayed response performance in Parkinson disease. Brain Cogn. 2008;67:1–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Hershey T, Wu J, Weaver PM. Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease. Exp Neurol. 2008;210:402–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Chuyan EN. Changes in motor asymmetry of low-intensive high-frequency electromagnetic radiation in normal conditions and under stress. Neurophysiology. 2005;37:164–8 [In Russian].CrossRefGoogle Scholar
  8. 8.
    Carlson JN, Stewens KD. Individual differences in ethanol self-administration following withdrawal are associated with asymmetric changes in dopamine and serotonin in the medial prefrontal cortex and amygdale. Alcohol Clin Exp Res. 2006;30:1678–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Tomer R, Goldshtein RZ, Wang GJ, et al. Incentive motivation is associated with striatal dopamine asymmetry. Biol Psychol. 2008;77:98–101.PubMedCrossRefGoogle Scholar
  10. 10.
    Belikova MV, Kolesnikova EE. Changes in rat striatum dopamine content under aging and dopamine insufficiency. Probl Aging Longevity. 2006;15:187–91 [In Russian].Google Scholar
  11. 11.
    Budilin S, Midzianovskaia IS, Shchegolevskii NV, et al. Asymmetry in the dopamine content in the nucleus accumbens and the motor preference in rats. Zh Vyssh Nerv Deiat Im I P Pavlova. 2007;57:598–603 [In Russian].PubMedGoogle Scholar
  12. 12.
    Tomer R, Aharon-Peretz J, Tsitrinbaum Z. Dopamine asymmetry interacts with medication to affect cognition in Parkinson’s disease. Neuropsychologia. 2007;45:357–67.PubMedCrossRefGoogle Scholar
  13. 13.
    Vernaleken I, Weibrich C, Siessmeier T, et al. Asymmetry in dopamine D (2/3) receptors of caudate nucleus is lost with age. Neuroimage. 2007;34:870–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Bee D, Pallot DJ. Acute hypoxic ventilation, carotid body cell division and dopamine content during early hypoxia in rats. J Appl Physiol. 1995;79:1504–11.PubMedGoogle Scholar
  15. 15.
    Nurse CA, Jackson A, Makintaire F, et al. Adaptation of O2 chemoreceptors to hypoxia in vitro. In: Women at altitude. Burlingron: Queen City Printers Inc.; 1997. p. 147–53.Google Scholar
  16. 16.
    Vrecko K, Storga D, Bikmayer JG, et al. NADH stimulates endogenous dopamine biosynthesis by enhancing the recycling of tetrahydrobiopterin in rat phaeochromocytoma cells. Biochem Biophys Acta. 1997;1361:59–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Serebrovskaya TV. Intermittent hypoxia research in the former Soviet Union and the commonwealth of the independent states (CIS): history and review of the concept and selective application. High Alt Med Biol. 2002;3:205–21.PubMedCrossRefGoogle Scholar
  18. 18.
    Bove J, Prou D, Perier C, et al. Toxin-induced models of Parkinson’s disease. NeuroRx. 2005;2:484–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Oleshko NN. Morphofunctional study of interaction of glutamate-, choline- and dopamine-ergic systems in neostriatum. Ross Fiziol Zh Im I M Sechenova. 1997;1–2:96–101 [In Russian].Google Scholar
  20. 20.
    Jacobowith PM, Richardson JS. Method for the rapid determination of norepinephrine, dopamine, serotonin in the same brain region. Pharmacol Biochem Behav. 1979;8:515–9.CrossRefGoogle Scholar
  21. 21.
    Stal’naya ID, Garishvili TG. Method malondialdehyde evaluation with help of tiobarbituric acid. In: Orekhovich VN, editor. Modern methods in biochemistry. Moscow: Medicine; 1977. p. 66–7 [In Russian].Google Scholar
  22. 22.
    Chevari S, Chaba I, Sekei Y. The role of super oxide dismutase in oxidative processes in the cella and the method of its estimation in biological materials. Lab Delo. 1985;11:678–81. [In Russian].PubMedGoogle Scholar
  23. 23.
    Korolyuk MA, Ivanova AI, Majorova IT, et al. Method of catalase activity examination. Lab Delo. 1988;1:16–9 [In Russian].Google Scholar
  24. 24.
    Calne DB, Reppard RF. Aging of nigrostriatal pathway in human. Can J Neurol Sci. 1987;14:424–7.PubMedGoogle Scholar
  25. 25.
    Hornykiewicz O. Neurochimical patology and the ethiology of Parkinson’s disease: basic facts and hipotetical possibilities. Mt Sinai J Med. 1988;5:11–20.Google Scholar
  26. 26.
    Betarbet R, Sherer TB, Greenmyre JT. Animal models of Parkinson’s disease. Bioessays. 2002;24:308–18.PubMedCrossRefGoogle Scholar
  27. 27.
    Kryzhanovski GN. Determinant structures in nervous system pathology. In: Generator mechanisms of neuropathological syndromes. Moscow; 1980. p. 360 [In Russian].Google Scholar
  28. 28.
    Kryzhanovski GN. General pathology of nervous system. Moscow; 1997, p. 352. [In Russian].Google Scholar
  29. 29.
    Chen J, Dinger B, Fidone SJ. Second messenger regulation of tyrosine hydroxilase gene expression in rat carotid body. Biol Signals. 1995;4:277–85.PubMedCrossRefGoogle Scholar
  30. 30.
    Millhorn DE, Conforti L, Beitner-Johnson D, et al. Regulation of ionic conductances and gene expression by hypoxia in an oxygen sensitive cell line. Adv Exp Med Biol. 1996;410:135–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Raymond R, Millhorn DE. Regulation of tyrosine hydroxylase gene expression during hypoxia: role of Ca2+ and PKC. Kidney Int. 1997;51:536–41.PubMedCrossRefGoogle Scholar
  32. 32.
    Lam SY, Tipoe GL, Long EC, et al. Differential expressions and roles of hypoxia-inducible factor-1alpha, -2alpha and -3alpha in the rat carotid body during chronic and intermittent hypoxia. Histol Histopathol. 2008;23:271–80.PubMedGoogle Scholar
  33. 33.
    Haavik J, Toska K. Tyrosine hydroxilase and Parkinson’s disease. Mol Neurobiol. 1998;16:285–309.PubMedCrossRefGoogle Scholar
  34. 34.
    Ponzio F, Brunello N, Algeri S. Catecholamine synthesis in brain of aging rat. J Neurochem. 1978;30:1617–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Tumer N, Larochelle JS. Tyrosine hydroxylase expression in rat adrenal medulla: influence of age and cold. Pharmacol Biochem Behav. 1995;51:775–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Lopez-Barneo J, Ortega-Saenz P, Pardal R, et al. Oxygen sensing in the carotid body. Ann N Y Acad Sci. 2009;1177:119–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Kolesnikova EE, Safronova OS, Serebrovskaya TV. Age-related peculiarities of breathing regulation and antioxidant enzymes under intermittent hypoxic training. J Physiol Pharmacol. 2003;54:20–4.PubMedGoogle Scholar
  38. 38.
    Rizvi SI, Maurya PK. Alterations in antioxidant enzymes during aging in humans. Mol Biotechnol. 2007;37:58–61.PubMedCrossRefGoogle Scholar
  39. 39.
    Gomes P, Simão S, Silva E, et al. Aging increases oxidative stress and renal expression of oxidant and antioxidant enzymes that are associated with an increased trend in systolic blood pressure. Oxid Med Cell Longev. 2009;2:138–45.PubMedCrossRefGoogle Scholar
  40. 40.
    Carvalho C, Santos MS, Baldeiras I, et al. Chronic hypoxia potentiates age-related oxidative imbalance in brain vessels and synaptosomes. Curr Neurovasc Res. 2010;7:288–300.PubMedCrossRefGoogle Scholar
  41. 41.
    Gautam N, Das S, Mahapatra SK, et al. Age associated oxidative damage in lymphocytes. Oxid Med Cell Longev. 2010;3:275–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Mann DMA, Yates PO. Possible role of neuromelanin in the pathogenesis of Parkinson’s disease. Mech Ageing Dev. 1983;21:193–203.PubMedCrossRefGoogle Scholar
  43. 43.
    Chiueh CC, Krishna G, Tulsi P, et al. Intracranial microdialysis of salicylic acid to detect hydroxyl radical generation through dopamine autooxidation in the caudate nucleus: effect of MPP+. Free Radic Biol Med. 1992;13:581–3.PubMedCrossRefGoogle Scholar
  44. 44.
    Boldyrev AA. Dual role of free radical oxygen forms in ischemic brain. Neirochimiya. 1995;12:3–13 [In Russian].Google Scholar
  45. 45.
    Dexter DT, Holley AE, Flitter WD, et al. Parkinson’s disease increased levels of hydroxyperoxides in the Parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord. 1994;9:92–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Yoritaka A, Hattori N, Uchida K, et al. Immunohistochemucal detection of 4-hydroxynonenal protein adducts in Parkinson’s disease. Proc Natl Acad Sci USA. 1996;93:2696–701.PubMedCrossRefGoogle Scholar
  47. 47.
    Serra JA, Domínguez RO, de Lustig ES, et al. Parkinson’s disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson’s, Alzheimer’s and vascular dementia patients. J Neural Transm. 2001;108:1135–48.PubMedCrossRefGoogle Scholar
  48. 48.
    Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson disease. Neurology. 1996;47:S161–70.PubMedCrossRefGoogle Scholar
  49. 49.
    Martilla RG, Lorentz H, Rinne UK. Oxygen toxicity, protecting enzymes in Parkinson’s disease: increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. J Neurol Sci. 1988;86:321–31.CrossRefGoogle Scholar
  50. 50.
    Yoritaka A, Hattori N, Mori H, et al. An immunohostochemical study on manganese superoxide dismutase in Parkinson’s disease. J Neurol Sci. 1997;148:181–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Smith TS, Bennet Jr JP. Mitochondrial toxins in models of neurodegenerative diseases. I. In vivo brain hydroxyl radical production during systemic MPTP treatment or following microialysis infusion of methylpyridinum or azide ions. Brain Res. 1997;765:183–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Yu YP, Ju WP, Li ZG, et al. Acupuncture inhibits oxidative stress and rotational behavior in 6-hydroxydopamine lesioned rat. Brain Res. 2010;1336:58–65.PubMedCrossRefGoogle Scholar
  53. 53.
    Gardner HW. Oxygen radical chemistry of polyunsaturated fatty acids. Free Radic Biol Med. 1989;7:65–86.PubMedCrossRefGoogle Scholar
  54. 54.
    Piretti MV, Pagliuca G. Systematic isolation and identification of membrane lipid oxidation products. Free Radic Biol Med. 1989;7:219–21.PubMedCrossRefGoogle Scholar
  55. 55.
    Davies KJA. Proteolytic systems as secondary antioxidant defenses. In: Chow CK, editor. Cellular antioxidant defense mechanisms. Boca Raton: CRC; 1988. p. 25–67.Google Scholar
  56. 56.
    Lindgren P, von Campenhausen S, Spottke E, et al. Cost of Parkinson’s disease in Europe. Eur J Neurol. 2005;12:68–73.PubMedCrossRefGoogle Scholar
  57. 57.
    Koutsilieri E, Scheller S, Grunblatt E, et al. Free radicals in Parkinson’s disease. J Neurol. 2002;2:II1–5.Google Scholar

Copyright information

© Springer-Verlag London 2012

Authors and Affiliations

  • Maria V. Belikova
    • 1
  • Evgenia E. Kolesnikova
    • 2
    Email author
  • Tatiana V. Serebrovskaya
    • 2
  1. 1.Medical Department, Kiev Medical University of Ukrainian Association of Folk MedicineAcademy of Medical Sciences of UkraineKievUkraine
  2. 2.Department of Hypoxic StatesBogomoletz Institute of Physiology National Academy of Sciences of UkraineKievUkraine

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