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Advances in Gerontology

, Volume 8, Issue 4, pp 302–308 | Cite as

Study of Age-Related Changes in Compensatory Processes in the Model of Neurodegeneration of the Nigrostriatal System in Rats

  • D. V. PlaksinaEmail author
  • I. V. Ekimova
Article
  • 4 Downloads

Abstract

It is generally accepted that old age is the main risk factor for the development and progression of Parkinson’s disease (PD). However, there is currently no data available that experimentally confirm the age dependence of the neurodegeneration progression rate and the activity of compensatory processes in the nigrostriatal system in the development of PD. The present study applies a model of nigrostriatal system neurodegeneration in rats of different ages, which was developed using the microinjections with proteasome inhibitor lactacystin (LC) into the substantia nigra pars compacta (SNpc). The model reproduces the main pathomorphological signs of PD with great reliability. It has been demonstrated that the administration of LC to old rats, compared to young and middle-aged ones, causes more pronounced neurodegenerative changes in the nigrostriatal system which are associated with impairments in fine motor function, a decrease in the growth of the stress-inducible heat shock protein Hsp70 in surviving neurons of SNpc, and a decrease in contents of tyrosine hydroxylase and the vesicular monoamine transporter 2. The data obtained suggest that the aging-related decrease in Hsp70 expression together with a decrease in the efficiency of compensatory processes is a significant factor which determines the progression of pathology in the nigrostriatal system in PD model in old rats. The age-related loss of compensatory mechanisms observed may be one of the causes of the rapid PD progression in the elderly.

Keywords:

aging Parkinson’s disease lactacystin neurodegeneration nigrostriatal system Hsp70 chaperone compensatory mechanisms rats 

Notes

REFERENCES

  1. 1.
    Anisimov, V.N., Molekulyarnye i fiziologicheskie mekhanizmy stareniya (Molecular and Physiological Mechanisms of Aging), St. Petersburg: Nauka, 2008, vol. 1.Google Scholar
  2. 2.
    Ekimova, I.V. and Plaksina, D.V., Effects of quercetin on neurodegenerative and compensatory processes in the nigrostriatal system in a model of the preclinical stage of Parkinson’s disease in rats, Neurosci. Behav. Physiol., 2017, vol. 47, no. 9, pp. 1029–1036.CrossRefGoogle Scholar
  3. 3.
    Ekimova, I.V., Plaksina, D.V., Guzhova, I.V., and Meshalkina, D.A., The role of inducible Hsp70 protein in modulation of neurodegenerative pathology in the nigrostriatal system typical to Parkinson’s disease, J. Evol. Biochem. Physiol., 2016, vol. 52, no. 1, pp. 80–83.CrossRefGoogle Scholar
  4. 4.
    Karpenko, M.N., Muruzheva, Z.M., Pestereva, N.S., and Ekimova, I.V., Infectious hypothesis of Parkinson’s disease, Ross. Fiziol. Zh. im. I.M. Sechenova, 2017, vol. 103, no. 8, pp. 841–853.Google Scholar
  5. 5.
    Pastukhov, Yu.F., Ekimova, I.V., and Chesnokova, A.Yu., Molecular mechanisms of the pathogenesis of Parkinson’s disease and preventive therapy, in Neirodegerativnye zabolevaniya: ot genoma do tselostnogo organizma. Chast’ 1. Motornaya funktsiya i ee regulyatsiya v norme i pri patologii (Neurodegenerative Diseases: From Genome until Whole Organism, Part 1: Motor Function and Its Regulation in Norm and Pathology), Moscow: Nauchnyi Mir, 2014, vol. 1, pp. 316–355.Google Scholar
  6. 6.
    Pastukhov, Yu.F., Chesnokova, A.Yu., Yakimchuk, A.A., et al., Changes in sleep during degeneration of neurons in the substantia nigra induced by the proteasome inhibitor lactacystin, Ross. Fiziol. Zh. im. I.M. Sechenova, 2010, vol. 96, no. 12, pp. 1190–1202.Google Scholar
  7. 7.
    Abramoff, M.D., Magalhaes, P.J., and Ram, S.J., Image processing with ImageJ, Biophotonics Int., 2004, vol. 11, no. 7, pp. 36–42.Google Scholar
  8. 8.
    Alexander, G.E., Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder, Dialogues Clin. Neurosci., 2004, vol. 6, no. 3, pp. 259–280.Google Scholar
  9. 9.
    Bentea, E., Verbruggen, L., and Massie, A., The proteasome inhibition model of Parkinson’s disease, J. Parkinson’s Dis., 2017, vol. 7, no. 1, pp. 31–63.CrossRefGoogle Scholar
  10. 10.
    Ciechanover, A. and Kwon, Y.T., Protein quality control by molecular chaperones in neurodegeneration, Front. Neurosci., 2017, vol. 11, p. 185.CrossRefGoogle Scholar
  11. 11.
    Ebrahimi-Fakhari, D., Wahlster, L., and McLean, P.J., Protein degradation pathways in Parkinson’s disease: curse or blessing, Acta Neuropathol., 2012, vol. 124, no. 2, pp. 153–172.CrossRefGoogle Scholar
  12. 12.
    Gonzalez, C. and Kolb, B., A comparison of different models of stroke on behavior and brain morphology, Eur. J. Neurosci., 2003, vol. 18, pp. 1950–1962.CrossRefGoogle Scholar
  13. 13.
    Hindle, J.V., Ageing, neurodegeneration and Parkinson’s disease, Age Ageing, 2010, vol. 39, pp. 156–161.CrossRefGoogle Scholar
  14. 14.
    Hsu, A.L., Murphy, C.T., and Kenyon, C., Regulation of aging and age-related disease by DAF-16 and heat shock factor, Science, 2003, vol. 300, pp. 1142–1145.CrossRefGoogle Scholar
  15. 15.
    Jankovic, J., Parkinson’s disease: clinical features and diagnosis, J. Neurol. Neurosurg. Psychiatry, 2008, vol. 79, no. 4, pp. 368–376.CrossRefGoogle Scholar
  16. 16.
    Jones, D.R., Moussaud, S., and McLean, P., Targeting heat shock proteins to modulate α-synuclein toxicity, Ther. Adv. Neurol. Disord., 2014, vol. 7, no. 1, pp. 33–51.CrossRefGoogle Scholar
  17. 17.
    Lopez-Otin, C., Blasco, M.A., Partridge, L., et al., The Hallmarks of Aging, Cell, 2013, vol. 153, no. 6, pp. 1194–1217.CrossRefGoogle Scholar
  18. 18.
    McNaught, K.S., Belizaire, R., Isacson, O., et al., Altered proteasomal function in sporadic Parkinson’s disease, Exp. Neurol., 2003, vol. 179, no. 1, pp. 38–46.CrossRefGoogle Scholar
  19. 19.
    Minoshima, S. and Cross, D., In vivo imaging of axonal transport using MRI: aging and Alzheimer’s disease, Eur. J. Nucl. Med. Mol. Imaging, 2008, vol. 35, suppl. 1, pp. S89–S92.CrossRefGoogle Scholar
  20. 20.
    Morimoto, R.I. and Cuervo, A.M., Proteostasis and the aging proteome in health and disease, J. Gerontol., A, 2014, vol. 69, suppl. 1, pp. S33–S38.Google Scholar
  21. 21.
    Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, San Diego: Academic, 1998.Google Scholar
  22. 22.
    Rudow, G., O’Brien, R., Savonenko, A.V., et al., Morphometry of the human substantia nigra in ageing and Parkinson’s disease, Acta Neuropathol., 2008, vol. 115, pp. 461–470.CrossRefGoogle Scholar
  23. 23.
    van Dyck, C.H., Seibyl, J.P., Malison, R.T., et al., Age-related decline in striatal dopamine transporter binding with iodine-123-β-CIT SPECT, J. Nucl. Med., 1995, vol. 36, no. 7, pp. 1175–1181.Google Scholar

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© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesSt. PetersburgRussia

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