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The role of adenosine A2A receptors of the preoptic area in somnogenic activity of 70 kDa protein in pigeons

  • Comparative and Ontogenic Physiology
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Abstract

The effects of adenosine A2A receptor antagonist microinjections into the hypothalamic ventrolateral preoptic area (VLPA) on the natural sleep-wake cycle and somnogenic activity of a 70 kDa heat shock protein (Hsp70) are analyzed electrophysiologically in birds, specifically, pigeons (Columba livia) for the first time. We report that: (1) at the beginning of the rest period, microinjections of 8-(3-Chlorostyryl)caffeine (ChC), an adenosine A2A receptor antagonist, into VLPA increase wake duration and inhibited sleep in a dose-dependent manner; (2) Hsp70 injections into VLPA evoke the somnogenic effect manifested as an increase in total slow-wave sleep (SWS) duration and enhancement of the mechanisms responsible for SWS triggering and maintenance; (3) ChC blockade of adenosine A2A receptors inhibits Hsp70-induced SWS. These data suggest that adenosine A2A receptors located in VLPA are involved in the modulation of the natural sleep-wake cycle and promotion of the Hsp70 somnogenic effect in pigeons. It is hypothesized that the somnogenic effect of Hsp70 is mediated by the modulating influence of this chaperone on the functioning of adenosine receptor proteins.

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References

  1. Nollen, E.A. and Morimoto, R.I., Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins, J. Cell Sci., 2002, vol. 115, pp. 2809–2816.

    CAS  PubMed  Google Scholar 

  2. Hunt, C. and Morimoto, R.I., Conserved features of eukaryotic HSP70 genes revealed by comparison with the nucleotide sequence of human HSP70, Proc. Natl. Acad. Sci. USA, 1985, vol. 82, pp. 6455–6459.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Pastukhov, Yu.F. and Ekimova, I.V., Molecular, cellular and systemic mechanisms of the protective function of the 70 Kda heat-shock protein, Neironauki, 2005, vol. 2, no. 2, pp. 3–25.

    Google Scholar 

  4. Margulis, B.A. and Guzhova, I.V., Dual role of chaperones in the response of a cell and of a whole organism to stress, Tsitologiya, 2009, vol. 51, no. 3, pp. 219–228.

    CAS  Google Scholar 

  5. Pastukhov, Yu.F., Khudik, K.A., and Ekimova, I.V., Chaperones in the regulation and restoration of physiological functions, Ros. Fiziol. Zh. im. Sechenova, 2010, vol. 96, no. 7, pp. 708–725.

    CAS  Google Scholar 

  6. Mackiewicz, M., Naidoo, N., Zimmerman, J.E., and Pack, A.I., Molecular mechanisms of sleep and wakefulness, Ann. N. Y. Acad. Sci., 2008, vol. 1129, pp. 335–349.

    Article  PubMed  Google Scholar 

  7. Pastukhov, Yu.F., Ekimova, I.V., Khudik, K.A., and Guzhova, I.V., Protein 70 Kda in the control of sleep and thermoregulation, J. Evol. Biochem. Physiol., 2008, vol. 44, no. 1, pp. 74–81.

    Article  CAS  Google Scholar 

  8. Ekimova, I.V., Nizinskya, L.E., Romanova, I.V., Pastukhov, Yu.F., Margulis, B.A., and Guzhova, I.V., Exogenous protein Hsp70 can penetrate into the brain structures and attenuate the severity of chemically-induced seizures, J. Neurochem., 2010, vol. 115, no. 4, pp. 1035–1044.

    Article  CAS  PubMed  Google Scholar 

  9. Ekimova, I.V., Somnogenic effect of exogenous heat shock protein 70 Kda is mediated by GABA(A) receptors in the preoptic area of the hypothalamus, Dokl. RAN, 2013, vol. 449, no. 6, pp. 89–92.

    CAS  Google Scholar 

  10. Obal, F., Jr. and Krueger, J.M., Biochemical regulation of non-rapid-eye-movement sleep, Front. Biosci., 2003, vol. 8, pp. 520–550.

    Article  Google Scholar 

  11. Kovalzon, V.M., Central mechanisms of the regulation of the sleep-wake cycle, Fiziol. Cheloveka, 2011, vol. 37, no. 4, pp. 124–134.

    CAS  Google Scholar 

  12. Sheth, S., Brito, R., Mukherjea, D., Rybak, L.P., and Ramkumar, V., Adenosine receptors: expression, function and regulation, Int. J. Mol. Sci., 2014, vol. 15, no. 2, pp. 2024–2052.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Fredholm, B.B., Astra award lecture. adenosine, adenosine receptors and the actions of caffeine, Pharmacol. Toxicol., 1995, vol. 76, pp. 93–101.

    Article  CAS  PubMed  Google Scholar 

  14. Portas, C.M., Thakkar, M., Rainnie, D.G., Greene, R.W., and McCarley, R.W., Role of adenosine in behavioral state modulation: a microdialysis study in the freely moving cat, Neuroscience, 1997, vol. 79, pp. 225–235.

    Article  CAS  PubMed  Google Scholar 

  15. Porkka-Heiskanen, T., Strecker, R.E., and Mc-Carley, R.W., Brain site specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study, Neuroscience, 2000, vol. 99, pp. 507–517.

    Article  CAS  PubMed  Google Scholar 

  16. Szymusiak, R., Alam, N., and McGinty, D., Discharge patterns of neurons in cholinergic regions of the basal forebrain during waking and sleep, Behav. Brain. Res., 2000, vol. 115, pp. 171–182.

    Article  CAS  PubMed  Google Scholar 

  17. Huang, Z.L., Urade, Y., and Hayaishi, O., The role of adenosine in the regulation of sleep, Curr. Top. Med. Chem., 2011, vol. 11, no. 8, pp. 1047–1057.

    Article  CAS  PubMed  Google Scholar 

  18. Sims, R.E., Wu, H.H., and Dale, N., Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study, PLoS One, 2013, vol. 8, no. 1:e53814, pp. 1–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Scammell, T.E., Gerashchenko, D.Y., Mochizuki, T., McCarthy, M.T., Estabrooke, I.V., Sears, C.A., Saper, C.B., Urade, Y., and Hayaishi, O., An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons, Neuroscience, 2001, vol. 107, pp. 653–663.

    Article  CAS  PubMed  Google Scholar 

  20. Methippara, M.M., Kumar, S., Alam, M.N., Szymusiak, R., and McGinty, D., Effects on sleep of microdialysis of adenosine A1 and A2a receptor analogs into the lateral preoptic area of rats, Am. J. Physiol. Regul. Integr. Comp. Physiol., 2005, vol. 289, no. 6, pp. R1715–R1723.

    Article  CAS  PubMed  Google Scholar 

  21. Kumar, S., Rai, S., Hsieh, K.C., McGinty, D., Alam, M.N., and Szymusiak, R., Adenosine A(2A) receptors regulate the activity of sleep regulatory gabaergic neurons in the preoptic hypothalamus, Am. J. Physiol. Regul. Integr. Comp. Physiol., 2013, vol. 305, no. 1, pp. R31–R41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Zhang, J., Yin, D., Wu, F., Zhang, G., Jiang, C., Li, Z., Wang, L., and Wang, K., Microinjection of adenosine into the hypothalamic ventrolateral preoptic area enhances wakefulness via the A1 receptor in rats, Neurochem. Res., 2013, vol. 38, no. 8, pp. 1616–1623.

    Article  CAS  PubMed  Google Scholar 

  23. Sarrió, S., Casadó, V., Escriche, M., Ciruela, F., Mallol, J., Canela, E.I., Lluis, C., and Franco, R., The heat shock cognate protein Hsc73 assembles with A(1) adenosine receptors to form functional modules in the cell membrane, Mol. Cell Biol., 2000, vol. 20, no. 14, pp. 5164–5174.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Karten, H.J. and Hodos, W.A., Stereotaxic Atlas of the Brain of the Pigeon (Columba livia), Johns Hopkins Press. Baltimore, Maryland, 1967, pp. 1–194.

    Google Scholar 

  25. Rashotte, M.E., Pastukhov, Iu.F., Poliakov, E.L., and Henderson, R.P., Vigilance states and body temperature during the circadian cycle in fed and fasted pigeons (Columba livia), Am. J. Physiol. Regul. Integr. Comp. Physiol., 1998, vol. 275, pp. R1690–R1702.

    CAS  Google Scholar 

  26. Sazanov, A.A., Molekulyarnaya organizatsiya genoma ptits (The Molecular Organization of Bird Genome), St.-Petersburg: LGU im. A.S. Pushkina, 2010.

    Google Scholar 

  27. Ivanov, A.A., Baskin, I.I., Palyulin, V.A., and Zefirov, N.S., Molecular modeling of adenosine receptors, Vestn. Mosk. Univ. Ser. 2. Khimiya, 2002, vol. 43, no. 4, pp. 231–236.

    CAS  Google Scholar 

  28. Sherin, J.E., Shiromani, P.J., McCarley, R.W., and Saper, C.B., Activation of ventrolateral preoptic neurons during sleep, Science, 1996, vol. 271(5246), pp. 216–219.

    Article  CAS  PubMed  Google Scholar 

  29. Saper, C.B., Scammell, T.E., and Lu, J., Hypothalamic regulation of sleep and circadian rhythms, Nature, 2005, vol. 437(7063), pp. 1257–1263.

    Article  CAS  PubMed  Google Scholar 

  30. Ekimova, I.V. and Pastukhov, Yu.F., Participation of gabaergic mechanisms of the hypothalamic ventrolateral preoptic area in the regulation of sleep-wake states and thermal homeostasis in pigeons Columba livia, Zh. Evol. Biokhim. Fiziol., 2005, vol. 41, no. 4, pp. 356–363.

    CAS  PubMed  Google Scholar 

  31. Hsu, C.C., Davis, K.M., and Jin, H., Association of L-glutamic acid decarboxylase to the 70-Kda heat shock protein as a potential anchoring mechanism to synaptic vesicles, J. Biol. Chem., 2000, vol. 275, no. 27, pp. 20822–20828.

    Article  CAS  PubMed  Google Scholar 

  32. Kelty, J.D., Noserworthy, P.A., Feder, M.E., Robertson, R.M., and Ramirez, J.M., Thermal preconditioning and heat-shock protein 72 preserve synaptic transmission during thermal stress, Neuroscience, 2002, vol. 22, no. 1, pp. 193–198.

    Google Scholar 

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Correspondence to I. V. Ekimova.

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Original Russian Text © I.V. Ekimova, Yu.F. Pastukhov, 2014, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2014, Vol. 50, No. 6, pp. 428–434.

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Ekimova, I.V., Pastukhov, Y.F. The role of adenosine A2A receptors of the preoptic area in somnogenic activity of 70 kDa protein in pigeons. J Evol Biochem Phys 50, 492–499 (2014). https://doi.org/10.1134/S0022093014060039

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  • DOI: https://doi.org/10.1134/S0022093014060039

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