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Disorders in the Cytoskeleton of Astroglia and Neurons in the Rat Brain Induced by Long-Lasting Exposure to Ethanol and Correction of These Shifts by Hydrated Fullerene С60

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Neurophysiology Aims and scope

Using an immunoblotting technique, we examined the content of proteins of intermediate filaments of the cytoskeleton of neurons and astroglial cells and also changes in the polypeptide composition of these proteins in different brain regions of rats subjected to long-term (12 weeks) alcoholization. The sensitivity of these indices to the effect of ethanol in different cerebral structures was in the following sequence: hippocampus > cerebral cortex > cerebellum. The greatest changes in a marker of the astrocyte cytoskeleton (glial fibrillary acidic protein, GFAP) were observed in the hippocampus of alcoholized animals, where the GFAP level was by 72% lower with respect to the control values. In this cerebral region, the content of the neurofilament 210-kdalton subunit also sharply dropped (by 76% with respect to the control). A positive correlation between a decrease in the GFAP content and loss of the neurofilament 210-kdalton subunit was demonstrated. These data show that the organization of the intracellular filamentary system of neurons and gliocytes is disturbed under experimental conditions, and this is one of the probable reasons for cell death in the nerve tissue induced by chronic consumption of ethanol. The use of a hydrated form of fullerene С60 (its molecular/colloid solution) for antioxidant correction of the pathological state of the CNS induced by the above-mentioned toxicant removed, to a considerable extent, negative modifications of cytoskeletal structures and protected astroglial and nerve cells from degeneration.

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References

  1. M. R. Freeman, “Sculpting the nervous system: glial control of neuronal development,” Curr. Opin. Neurobiol., 16, 119–125 (2006).

    Article  PubMed  CAS  Google Scholar 

  2. T. Makar, M. Nedergaard, A. Preuss, et al., “Vitamin E, ascorbate, glutathione disulfide and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain,” J. Neurochem., 62, 45–53 (1994).

    Article  PubMed  CAS  Google Scholar 

  3. L. Allanson, S. Khatibi, T. Olsson, and E. Hansson, “Acute ethanol exposure induces [Ca2+] i transients, cell swelling, and transformation of actin cytoskeleton in astroglial primary cultures,” J. Neurochem., 76, 472–479 (2001).

    Article  Google Scholar 

  4. T. Fellin and G. Carmignoto, “Neuron-to-astrocyte signalling in the brain represents a distinct multifunctional unit,” J. Physiol., 559, 3–15 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. L. Korbo, “Glial cell loss in the hippocampus of alcoholics,” Alcohol. Clin. Exp. Res., 23, 164–168 (1999).

    PubMed  CAS  Google Scholar 

  6. S. Goldman, “Glia as neural progenitor cells,” Trends Neurosci., 26, 590–596 (2003).

    Article  PubMed  CAS  Google Scholar 

  7. A. J. Eisch, M. Barrot, C. A. Schad, et al., “Opiates inhibit neurogenesis in the adult rat hippocampus,” Proc. Natl. Acad. Sci. USA, 97, 7579–7584 (2000).

    Article  PubMed  CAS  Google Scholar 

  8. M. Ohgoh, H. Shimizu, H. Ogura, and J. Nishizawa, “Astroglial trophic support and neuronal cell death: influence of cellular energy level on type of cell death induced by mitochondrial toxin in cultured rat cortical neurons,” J. Neurochem., 75, 925–933 (2000).

    Article  PubMed  CAS  Google Scholar 

  9. L. F. Eng, R. S. Ghirnikar, and Y. L. Lee, “Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000),” Neurochem. Res., 25, Nos. 910, 1439–1451 (2000).

    Article  PubMed  CAS  Google Scholar 

  10. R. K. Liem, “Molecular biology of neuronal intermediate filament,” Curr. Opin. Cell Biol., 5, 12–16 (1993).

    Article  PubMed  CAS  Google Scholar 

  11. S. G. Evrard, M. Duhalde-Vega, P. Tagliaferro, et al., “A low chronic exposure induces morphological changes in the adolescent rat brain that are not fully recovered even after a long abstinence: an immunohistochemical study,” Exp. Neurol., 200, 438–459 (2006).

    Article  PubMed  CAS  Google Scholar 

  12. C. E. Teunissen, H. W. Steinbusch, M. Angevaren, et al., “Behavioral correlates of striatal glial fibrillary acidic protein in the 3-nitropropionic acid rat model: disturbed walking pattern and spatial orientation,” Neuroscience, 105, 153–167 (2001).

    Article  PubMed  CAS  Google Scholar 

  13. H. W. Kroto, S. Heath, S. C. O’Brien, et al., “C60: Buckminsterfullerene,” Nature, 318, 162 (1985).

    Article  CAS  Google Scholar 

  14. L. B. Piotrovskii and O. I. Kiselev, Fullerenes in Biology [in Russian], Rostok, Saint Petersburg, (2006).

    Google Scholar 

  15. I. Wang, L. Tai, D. Lee, et al., “C60 and water-soluble fullerene derivatives as antioxidants against radicalinitiated lipid peroxidation,” J. Med. Chem., 42, 4614– 4620 (1999).

    Article  PubMed  CAS  Google Scholar 

  16. A. A. Tikhomirov, V. S. Nedzvetskii, M. V. Lipka, et al., “Chronic alcoholization-induced damage to astroglia and intensification of lipid peroxidation in the rat brain: protector effect of hydrated form of fullerene C60,” Neurophysiology, 39, No. 2, 105–111 (2007).

    Article  CAS  Google Scholar 

  17. G. V. Andrievsky, M. V. Kosevich, O. M. Vovk, et al., “On the production of an aqueous colloidal solution of fullerenes,” J. Chem. Soc. Chem. Commun., 12, 1281–1282 (1995).

    Article  Google Scholar 

  18. M. V. Avdeev, A. A. Khokhryakov, T. V. Tropin, et al., “Structural features of molecular-colloidal solutions of C60 fullerenes in water by small-angle neutron scattering,” Langmuir, 20, 4363–4368 (2004).

    Article  PubMed  CAS  Google Scholar 

  19. G. V. Andrievsky, V. K. Klochkov, E. L. Karyakina, and N. O. Mchedlov-Petrossyan, “Studies of aqueous colloidal solutions of fullerene C60 by electron microscopy,” Chem. Phys. Lett., 300, 392–396 (1999).

    Article  CAS  Google Scholar 

  20. A. D. Roslyakov, G. V. Andrievsky, A. Yu. Petrenko, L. T. Malaya, “Cytotoxic and antioxidant properties of aqueous solutions of native fullerenes in in vitro systems,” Zh. Akad. Med. Nauk Ukrainy, 5, 338–346 (1999).

    Google Scholar 

  21. G. V. Andrievsky, V. K. Klochkov, A. Bordyuh, and G. I. Dovbeshko, “Comparative analysis of two aqueouscolloidal solutions of C60 fullerene with help of FT-IR reflectance and UV-Vis spectroscopy,” Chem. Phys. Lett., 364, 8–17 (2002).

    Article  CAS  Google Scholar 

  22. G. V. Andrievsky, V. K. Klochkov, and L. I. Derevyanchenko, “Is C60 fullerene molecule toxic?!” Fuller., Nanotub. Carbon Nanostruct., 13, 363–376 (2005).

    Article  CAS  Google Scholar 

  23. A. Jensen, S. Wilson, and D. Schuster, “Biological application of fullerenes – a review,” Bioorg. Med. Chem. Lett., 4, 767–779 (1996).

    Article  CAS  Google Scholar 

  24. R. V. Bensasson, M. Brettreich, J. Frederiksen, et al., “Reactions of e−(aq), CO2 •−, HO•−, O2 •− and O2 (1∆g) with a dendro[60]fullerene and C60[C(COOH)2]n (n = 2–6),” Free Radical Biol. Med., 29, 26–33 (2000).

    Article  CAS  Google Scholar 

  25. S. Bosi, T. Da Ros, G. Spalluto, and M. Prato, “Fullerene derivatives: an attractive tool for biological applications (invited review),” Eur. J. Med. Chem., 38, 913–923 (2003).

    Article  PubMed  CAS  Google Scholar 

  26. S. S. Ali, J. I. Hardt, K. L. Quick, et al., “A biologically effective fullerene (C60) derivative with superoxide dismutase mimetic properties,” Free Radical Biol. Med., 37, 1191–1202 (2004).

    Article  CAS  Google Scholar 

  27. A. Isakovic, Z. Markovic, N. Nikolic, et al., “Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation,” Biomaterials, 27, 5049–5058 (2006).

    Article  PubMed  CAS  Google Scholar 

  28. J. J. Ryan, H. R. Bateman, A. Stover, et al., “Fullerene nanomaterials inhibit the allergic response,” J. Immunol., 179, 665–672 (2007).

    PubMed  CAS  Google Scholar 

  29. M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding,” Analyt. Biochem., 72, 248–254 (1976).

    Article  PubMed  CAS  Google Scholar 

  30. V. S. Nedzvetsky and P. O. Nerush, “The protein of glial intermediate filaments in different areas of the rat brain at experimental neurosis,” Neurophysiology, 31, No. 2, 94–97 (1999).

    Article  Google Scholar 

  31. D. E. Saunders, J. A. Di Cerbo, J. R. Williams, and J. H. Hannigan, “Alcohol reduces neurofilament protein levels in primary cultured hippocampal neurons,” Alcohol, 14, 519–526 (1997).

    Article  PubMed  CAS  Google Scholar 

  32. K. Iwamoto, M. Bundo, M. Yamamoto, et al., “Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics,” Neurosci. Res., 49, 379–385 (2004).

    Article  PubMed  CAS  Google Scholar 

  33. R. A. Nixon and T. B. Shea, “Dynamics of neuronal intermediate filaments: a developmental perspective,” Cell Motil. Cytoskeleton, 22, 81–91 (1992).

    Article  PubMed  CAS  Google Scholar 

  34. H. Franke, H. Kittner, P. Berger, et al., “The reaction of astrocytes and neurons in the hippocampus of adult rats during chronic ethanol treatment and correlations to behavioral impairments,” Alcohol, 14, 445–454 (1997).

    Article  PubMed  CAS  Google Scholar 

  35. J. J. Miguel-Hidalgo, “Lower packing density of glial fibrillary acidic protein-immunoreactive astrocytes in the prelimbic cortex of alcohol-naive and alcoholdrinking alcohol-preferring rats as compared with alcohol nonpreferring and Wistar rats,” Alcohol. Clin. Exp. Res., 29, 766–772 (2005).

    Article  PubMed  CAS  Google Scholar 

  36. S. M. Mooney and M. W. Miller, “Ethanol-induced neuronal death in organotypic cultures of rat cerebral cortex,” Dev. Brain Res., 147, 135–141 (2003).

    Article  CAS  Google Scholar 

  37. B. Seri, J. M. Garcia-Verdugo, B. S. McEwen, and A. Alvarez-Buylla, “Astrocytes give rise to new neurons in the adult mammalian hippocampus,” J. Neurosci., 21, 7153–7160 (2001).

    PubMed  CAS  Google Scholar 

  38. A. Y. Sun, M. Ingelman-Sunberg, E. Neve, et al., “Ethanol and oxidative stress,” Alcohol. Clin. Exp. Res., 25, 237–243 (2001).

    Google Scholar 

  39. L. L. Dugan, E. G. Lovett, K. L. Quick, et al., “Fullerenebased antioxidants and neurodegenerative disorders,” Parkinson. Relat. Disord., 7, 243–246 (2001).

    Article  Google Scholar 

  40. A. M.-Y. Lin, S. F. Fang, S. Z. Lin, et al., “Local carboxyfullerene protects cortical infarction in rat brain,” Neurosci. Res., 43, 317–321 (2002).

    Article  PubMed  CAS  Google Scholar 

  41. I. Y. Podolski, Z. A. Podlubnaya, E. A. Kosenko, et al., “Effects of hydrated forms of C60 fullerene on amyloid β-peptide fibrillization in vitro and performance of the cognitive task,” J. Nanosci. Nanotech., 7, Nos. 4/5, 1479–1485 (2007).

    Article  CAS  Google Scholar 

  42. K. L. Quick, S. S. Ali, R. Arch, et al., “A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice,” Neurobiol. Aging, 29, 117–128 (2008).

    Article  PubMed  CAS  Google Scholar 

  43. T. Mori, S. Ito, M. Namiki, et al., “Involvement of free radical followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: comparison of the therapeutic potential of fullerene, mepacrine, and cooling,” Toxicology, 236, 149–157 (2007).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dnepropetrovsk National University, Dnepropetrovsk, Ukraine

    А. A. Tikhomirov & V. S. Nedzvetsky

  2. ІСМА, NTK “Institute of Monocrystals”, National Academy of Sciences of Ukraine, Khar’kov, Ukraine

    G. V. Andrievsky

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  1. А. A. Tikhomirov
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  2. G. V. Andrievsky
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  3. V. S. Nedzvetsky
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Correspondence to А. A. Tikhomirov.

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Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 331–339, July–August, 2008.

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Tikhomirov, А.A., Andrievsky, G.V. & Nedzvetsky, V.S. Disorders in the Cytoskeleton of Astroglia and Neurons in the Rat Brain Induced by Long-Lasting Exposure to Ethanol and Correction of These Shifts by Hydrated Fullerene С60 . Neurophysiology 40, 279–287 (2008). https://doi.org/10.1007/s11062-009-9044-9

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