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cDNA macroarray analysis of gene expression changes in rat brain after a single administration of a 2-aminoadamantane derivative

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Abstract

The Atlas™ Rat cDNA Expression Array (BD Biosciences, United States) has been used to analyze changes in the expression of 588 genes in rat brain cells in response to a single administration of Ladasten, a 2-aminoadamantane derivative that has psychostimulating and anxiolytic effects. The analysis of hybridization on macroarrays, confirmed by the results of real-time quantitative RT-PCR, has demonstrated that Ladasten alters the expression of 12 genes in the rat brain. The GAT3 and CARBH genes are presumed to be pharmacologically important targets of Ladasten. The changes in their activity explain the mechanisms of the anxiolytic and mood-stabilizing effects of the drug. Ladasten has been shown to induce the genes whose products are involved in various signal pathways (APC, Rb, PKCIP, and PMCA), as well as the genes of cytoskeletal proteins (Tubα1 and actin), synaptic proteins (SynIA&IB and PLP), and enzymes (Gapdh and NSE). The proteins encoded by these genes are presumably involved in compensatory and/or neuroplastic adaptation to the effects of Ladasten.

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REFERENCES

  1. Morozov I.S., Artsimovich I.G., Fadeeva T.A. 1993. USSR Patent 1826906. Byull. Izobret. 25, 97.

    Google Scholar 

  2. Morozov I.S., Klimova N.V., Sergeeva S.A., Ivanova I.A., Barchukov V.G., Kovalev G.I., Pyatin B.M., Avdyunina N.I. 1999. Adamantane derivatives improving resistance to extreme influences. Vestn. Ross. Akad. Med. Nauk. 23, 28–32.

    Google Scholar 

  3. Morozov I.S., Efimova L.P., Salenko Yu.A. 2000. Effects of bromantane and Sydnocarb on the efficiency of longterm operant activity and its vegetative correlates in rats. Eksp. Klin. Farmakol. 63, 11–15.

    CAS  PubMed  Google Scholar 

  4. Morozov I.S., Petrov V.I., Sergeeva S.A. 2001. Farmakologiya adamantanov (Pharmacology of Adamantane and Its Derivatives), Volgograd.

  5. Kudrin V.S., Sergeeva S.A., Krasnykh L.M., Miroshnichenko I.I., Grekhova T.V., Gainetdinov R.R. 1995. Effect of bromantane on dopamin-and serotoninegric systems of the rat brain. Eksp. Klin. Farmakol. 58, 8–11.

    CAS  Google Scholar 

  6. Yarkova M.A., Voronin M.V., Morozov I.S. 2001. Abstr. 3rd Int. Conf. “Biological Basis of Individual Sensitivity to Psychotropic Drugs,” Suzdal, 2001, p. 169.

  7. Grekhova T.V., Gainetdinov R.R., Sotnikova T.D., Krasnykh L.M., Kudrin V.S., Sergeeva S.A., Morozov I.S. 1995. Influence of bromantane, a new immunostimulant with a psychostimulating effect, on dopamine release and metabolism in the dorsal striatum of free-moving rats: A microdialysis analysis. Byull. Eksp. Biol. Med. 3, 302–304.

    Google Scholar 

  8. Vakhitova Yu.V., Yamidanov R.S., Seredenin S.B. 2004. Ladasten induces the expression of genes regulating dopamine synthesis in different structures of the rat brain. Eksp. Klin. Farmakol. 67, 7–11.

    Google Scholar 

  9. Guang Ch., Khondakar A., Hasanat A., Bebchuk J.M., Moore G., Clitz D., Manji H.K. 1999. Regulation of signal transduction pathways and gene expression by mood stabilizers and antidepressants. Psychosomatic Med. 61, 599–617.

    Google Scholar 

  10. Vakhitova Yu.V., Salimgareeva M.Kh., Seredenin S.B. 2004. Effect of Ladasten on protein kinase C activity in rat brain cells. Eksp. Klin. Farmakol. 67, 12–15.

    CAS  Google Scholar 

  11. Vakhitova Yu.V., Salimgareeva M.Kh., Seredenin S.B. 2004. Effect of Ladasten on the activity of sAMP-dependent protein kinases and protein phosphorylation in rat brain cells. Eksp. Klin. Farmakol. 67, 7–9.

    Google Scholar 

  12. Applied Biosystems, ABI PRISM 7700 Sequence Detection System, User Bulletin no. 2, 2001.

  13. Pfaffl M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, E45.

    Article  CAS  PubMed  Google Scholar 

  14. Freeman W.M., Robertson D.J., Vrana K.E. 2000. Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression. Biotechniques. 29, 1042–1055.

    CAS  PubMed  Google Scholar 

  15. Freeman W.M., Brebner K., Lynch W.J., Palet K.M., Robertson D.J., Roberts D.C.S., Vrana K.E. 2002. Changes in rat frontal cortex gene expression following chronic cocaine. Mol. Brain Res. 104, 11–20.

    Article  CAS  PubMed  Google Scholar 

  16. Sokolov B.P., Polesskaya O.O., Uhl G.R. 2003. Mouse brain gene expression changes after acute and chronic amphetamine. J. Neurochem. 84, 244–252.

    Article  CAS  PubMed  Google Scholar 

  17. Jayanthi S., McCoy M.T., Ladenheim B., Cadet J.L. 2002. Methamphetamine causes coordinate regulation of Src, Cas, Crk and Jun N-terminal kinase-Jun pathway. Mol. Pharmacol. 61, 1124–1131.

    CAS  PubMed  Google Scholar 

  18. Freeman W.M., Brebner K., Lynch W.J., Robertson D.J., Roberts D.C.S., Vrana K.E. 2001. Cocaine-responsive gene expression changes in rat hippocampus J. Neurosci. 108, 371–380.

    CAS  Google Scholar 

  19. Dringen R., Gebhardt R., Hamprecht B. 1993. Glycogen in astrocytes: Possible function as lactate supply for neighboring cells. Brain Res. 623, 208–214.

    CAS  PubMed  Google Scholar 

  20. Marangos P.J., Schmechel D.E. 1987. Neuron-specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu. Rev. Neurosci. 10, 269–295.

    CAS  PubMed  Google Scholar 

  21. Hattori T., Takei N., Mizuno Y., Kato K., Kohsaka S. 1995. Neurotrophic and neuroprotective effects of neuron-specific enolase on cultured neurons from embryonic rat brain. Neurosci. Res. 21, 191–198.

    CAS  PubMed  Google Scholar 

  22. Dastoor Z., Dreyer J.L. 2001. Potential role of nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase in apoptosis and oxidative stress. J. Cell Sci. 114, 1643–1653.

    CAS  PubMed  Google Scholar 

  23. Allaman I., Pellrin L., Magistrelli P.J. 2000. Protein targeting to glycogen (PTG) mRNA expression is stimulated by noradrenaline in mouse cortical astrocytes. Glia. 30, 282–391.

    Google Scholar 

  24. Akil H., Owens C., Gutstein H. 1998. Endogenous opioids: Overview and current issues. Drug Alcohol. Depend. 51, 127–140.

    CAS  PubMed  Google Scholar 

  25. Kiefler B.L. 1995. Recent advances in molecular recognition and signal transduction of active peptides: Receptors for opioid peptides. Cell. Mol. Neurobiol. 15, 615–634.

    PubMed  Google Scholar 

  26. Khaidarliu S.Kh. 1989. Neiromediatornye mekhanizmy adaptatsii (Neurotransmitter-Related Mechanisms of Adaptation). Chisinau.

  27. Khalimov A.R., Nasyrov Kh.M., Sergeeva S.A. 1997. Effect of bromantane on serum cortisol and insulin levels. Zdravookhr. Bashkir. 3, 7–10.

    Google Scholar 

  28. Hook V.Y.H., LaGamma E.F. 1987. Product inhibition of carboxypeptidase H. J. Biol. Chem. 262, 12583–12588.

    CAS  PubMed  Google Scholar 

  29. Rodriguez C., Braybon K.A., Brownstein M., Dixon J.E. 1984. Rat preprocarboxypeptidase H: Cloning, characterization, and sequence of the cDNA and regulation of the mRNA by corticotropin-releasing factor. J. Biol. Chem. 264, 5988–5995.

    Google Scholar 

  30. Berke J.D., Paletzki R.F., Aronson G.J., Hyman S.E., Gerfen C.R. 1998. A complex program of striatal gene expression induced by dopaminergic stimulation. J. Neurosci. 18, 5301–5310.

    CAS  PubMed  Google Scholar 

  31. Masson J., Sagne C., Hamon M., Mestikawys E. 1999. Neurotransmitter transporters in the central nervous system. Pharmacol. Rev. 51, 439–464.

    CAS  PubMed  Google Scholar 

  32. Voronina T.A., Seredenin S.B. 2002. Perspectives in the search for new anxiolytic drugs. Eksp. Klin. Farmakol. 5, 4–17.

    Google Scholar 

  33. Peng W., Simantov R. 2003. Altered gene expression in frontal cortex and midbrain of 3,4-methylene-dioxymethamphetamine (MDMA) treated mice: Differential regulation of GABA transporter subtypes. J. Neurosci. Res. 72, 250–258.

    CAS  PubMed  Google Scholar 

  34. Ito C. 2002. Analysis of overall gene expression induced by amphetamine and phencyclidine: Novel targets for the treatment of drug psychosis and schizophrenia. Curr. Pharmaceut. Design. 8, 147–153.

    CAS  Google Scholar 

  35. Seredenin S.B., Miramedova A.G. 1999. Analysis of the spectrum of pharmacological properties of bromantane. Bull. Eksp. Biol. Med. 128, 529–531.

    CAS  Google Scholar 

  36. Boggs J.M., Mosarello M.A. 1978. Structural organization of the human myelin membrane. Biochim. Biophys. Acta. 515, 1–21.

    CAS  PubMed  Google Scholar 

  37. MacMillan S.V., Ishiyma N., White G.F., Palaniyar N., Hallett F.R., Harauz G. 2000. Myelin basic protein component C1 in increasing concentrations can elicit fusion, aggregation, and fragmentation of myelin-like membranes. Eur. J. Cell Biol. 79, 327–335.

    CAS  PubMed  Google Scholar 

  38. Kaplan M.R., Meyer-Franke A., Lambert S., Bennett V., Duncan I.D., Levinson S.R., Barres B.A. 1997. Induction of sodium channel clustering by oligodendrocytes. Nature. 386, 724–728.

    CAS  PubMed  Google Scholar 

  39. Greengard P., Valtorta F., Czernik A.J., Benfenati F. 1993. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science. 259, 780–785.

    CAS  PubMed  Google Scholar 

  40. Thiriet N., Ladenheim B., McCoy M.T., Cadet J.L. 2002. Analysis of Ecstasy (MDMA)-induced transcriptional responses in the rat cortex. FASEB J. 16, 1887–1894.

    CAS  PubMed  Google Scholar 

  41. Wong M.-L., O’Kirwan F., Hannestad J.P., Irizarry K.J.L., Elashoff D., Licinio J. 2004. St John’s wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response. Mol. Psych. 9, 237–251.

    CAS  Google Scholar 

  42. Noailles D.A., Becher K.G., Wood W.H., Teichberg D., Cadet J.L. 2003. Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero. Brain Res. Dev. Brain Res. 147, 153–162.

    CAS  PubMed  Google Scholar 

  43. Yaffe M.B. 2002. How do 14-3-3 proteins work? Gatekeeper phosphorylation and the molecular anvil hypothesis. FEBS Lett. 513, 53–57.

    CAS  PubMed  Google Scholar 

  44. Carafoli E. 2002. Calcium signaling: A tale for all seasons. Proc. Natl. Acad. Sci. USA. 99, 1115–1122.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia

    Yu. V. Vakhitova & S. B. Seredenin

  2. Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054, Bashkortostan, Russia

    Yu. V. Vakhitova, R. S. Yamidanov & V. A. Vakhitov

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  1. Yu. V. Vakhitova
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  2. R. S. Yamidanov
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  3. V. A. Vakhitov
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  4. S. B. Seredenin
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__________

Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 276–285.

Original Russian Text Copyright © 2005 by Vakhitova, Yamidanov, Vakhitov, Seredenin.

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Vakhitova, Y.V., Yamidanov, R.S., Vakhitov, V.A. et al. cDNA macroarray analysis of gene expression changes in rat brain after a single administration of a 2-aminoadamantane derivative. Mol Biol 39, 244–252 (2005). https://doi.org/10.1007/s11008-005-0035-7

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