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Participation of agouti-related peptide in the regulation of the wakefulness-sleep cycle

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Abstract

Agouti-related peptide is expressed in the hypothalamic neurons in humans and animals. Immunohistochemical studies in Wistar rats shows significant changes in the optical density of agouti-related peptide in the neurons of the arcuate hypothalamic nucleus, as well as in their processes in the hypothalamus and nucleus accumbens after 6 h of sleep deprivation (an increase) and after 2 h of post-deprivative sleep (a decrease). Comparison of these findings with the earlier results shows the opposite trends in the changes in the optical density of agouti-related peptide and the speed of the limiting enzyme of dopamine synthesis, tyrosine hydroxylase, in the hypothalamus and in the striatonigral system. An increase in the agouti-related peptide level was accompanied by a decrease in tyrosine hydroxylase, while a decrease in agouti-related peptide, on the contrary, was accompanied by an increase in the tyrosine hydroxylase activity. Our data show the role played by agouti-related peptide as a modulator of the functional activity of the dopaminergic brain neurons. The interrelation between various functions of the body, such as food behavior, sleep, and stress, is considered to be mediated by the participation of the same neurotransmitter systems in their regulation.

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References

  1. Ollmann, M., Wilson, B., Yang, Y., Kerns, J., Chen, Y., Gantz, I., and Barsh, G., Effects of recombinant agouti-signaling protein on melanocortin action, Science, 1997, vol. 278, p. 135.

    Article  PubMed  CAS  Google Scholar 

  2. Siljee, J.E., Unmehopa, U.A., Kalsbeek, A., Swaab, D.F., Fliers, E., and Alkemade, A., Melanocortin 4 receptor distribution in the human hypotthalamus, Eur. J. Endocrinol., 2013, vol. 168, no. 3, p. 361.

    Article  PubMed  CAS  Google Scholar 

  3. Bagnol, D., Lu, X.Y., Kaelin, C.B., Day, H.E., Olmann, M., Gantz, I., Barsh, G.S., and Watson, S.J., Anatomy of an endogenous antagonist: relationship between agouti-related protein and proopiomelanocortin in brain, J. Neurosci., 1999, vol. 19, p. 1.

    Google Scholar 

  4. Yang, Y.K., Ollmann, M., Wilson, B., Dickinson, C., Yamada, T., Barsh., and Gantz, I., Effects of recombinant agouti-signaling protein on melanocortin action, Mol. Endocrinol., 1997, vol. 11, p. 274.

    Article  PubMed  CAS  Google Scholar 

  5. Goldstone, A.P., Unmehopa, U.A., Bloom, S.R., and Swaab, D.F., Hypothalamic NPY and agouti-related protein are increased in human illness but not in Prader-Willi syndrome and other obese subjects, J. Clin. Endocrinol. Metab., 2002, vol. 87, no. 2, p. 927.

    Article  PubMed  CAS  Google Scholar 

  6. Tolle, V. and Low, M.J., In vivo evidence for inverse agonism of agouti-related peptide in the central nervous system of proopiomelanocortin-deficient mice, Diabetes, 2008, vol. 57, no. 1, p. 86.

    Article  PubMed  CAS  Google Scholar 

  7. Pritchard, L.E. and White, A., Agouti-related protein: More than a melanocortin-4 receptor antagonist?, Peptides, 2005, vol. 26, p. 1759.

    Article  PubMed  CAS  Google Scholar 

  8. Romanova, I.V., The role of CART and AGRP in modulation of functional activity of dopaminergic neurons of the brain, Extended Abstract of Doctoral (Med.) Dissertation, St. Petersburg, 2012, 42 p.

    Google Scholar 

  9. Ugryumov, M.V., Mekhanizmy neiroendokrinnoi regulyatsii (Mechanisms of Neuroendocrinal Regulation), Moscow: Nauka, 1999.

    Google Scholar 

  10. Charbonneau, C., Bai, F., Richards, B.S., and Argyropoulos, G., Central and peripheral interactions between the agouti-related protein and leptin, Biochem. Biophys. Res. Commun., 2004, vol. 319, no. 2, p. 518.

    Article  PubMed  CAS  Google Scholar 

  11. Oganesyan, G.A., Aristakesyan, E.A., Belova, V.A., Artamokhina, I.V., and Romanova, I.V., Dopaminergic nigrostriatal system during sleep deprivation in rats, Ross. Fiziol. Zh. im. I. M. Sechenova, 2007, vol. 93, no. 12, p. 1344.

    CAS  Google Scholar 

  12. Oganesyan, G.A., Romanova, I.V., Aristakesyan, E.A., Kuzik, V.V., Makina, D.M., Morina, I. Yu., Khramenkova, A.V., Artamokhina, I.V., and Belova, V.A., Diencephalon-telencephalon changes of the activity of tyrosine hydroxylase in rats and grass frogs during sleep deprivation, Zh. Evol. Biokhim. Fiziol., 2008, vol. 44, no. 3, p. 250.

    Google Scholar 

  13. Paxinos, G. and Watson, Ch., The Rat Brain in Stereotaxic Coordinates, San Diego: Academic Press, 1998, 4th edition.

    Google Scholar 

  14. Kheriet, E.R. and Gatter, K.S., Immunocytichemistry: Optical microscopy, in Molekulyarnaya klinicheskaya diagnostika. Metody (Molecular Clinic Diagnostics: Methods), Moscow, 1999, p. 20.

    Google Scholar 

  15. Gvilia, I., Turner, A., McGinty, D., and Szymusiak, R., Preoptic area neurons and the homeostatic regulation of rapid eye movement sleep, J. Neurosci., 2006, vol. 26, p. 3037.

    Article  PubMed  CAS  Google Scholar 

  16. Koval’zon, V.M., Osnovy somnologii. Fiziologiya i neirokhimiya tsikla bodrstvovanie-son mlekopitayushchikh (The Basics of Somnology. Physiology and Neurochemistry of the Sleep-Wakefulness Cycle in Mammals), Moscow: Binom: Laboratoriya Znanii, 2011.

    Google Scholar 

  17. Koban, M., Le, W.W., and Hoffman, G.E., Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats, Endocrinology, 2006, vol. 147, no. 1, p. 421.

    Article  PubMed  CAS  Google Scholar 

  18. Ranjbaran, Z., Keefer, L., Stepanski, E., Farhadi, A., and Keshavarzian, A., The relevance of sleep abnormalities to chronic inflammatory conditions, Inflamm. Res., 2007, vol. 56, no. 2, p. 51.

    Article  PubMed  CAS  Google Scholar 

  19. Guo, J.S., Chau, J.F.L., Cho, C.H., and Koo, M.W.L., Partial sleep deprivation compromises gastric mucosal integrity in rats, Life Sci., 2005, vol. 77, no. 2, p. 220.

    Article  PubMed  CAS  Google Scholar 

  20. Stanley, S.A., Small, C.J., Murphy, K.G., Murphy, K.G., Rayes, E., Abbot, C.R., Seal, L.G., Morgan, D.G., Sunter, D., Dakin, C.L., Kim M.S., Hunter, R., Kuhar, M., Ghatei, M.A., and Bloom, S.R., Actions of cocaine- and amphetamine-regulated transcript (cart) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats, Brain Res., 2001, vol. 893, p. 186.

    Article  PubMed  CAS  Google Scholar 

  21. Schwartz, M.W. and Morton, G.J., Obesity: keeping hunger at bay, Nature, 2002, vol. 418, p. 595.

    Article  PubMed  CAS  Google Scholar 

  22. Koban, M., Sita, L.V., Le W.W., and Hoffman G.E., Sleep deprivation of rats: the hyperphagic response is real, Sleep, 2008, vol. 31, no. 7, p. 927.

    PubMed  Google Scholar 

  23. Romanova, I.V., Morphofunctional interaction of the CART-peptide and dopaminergic neurons of the brain, Zh. Evol. Biokhim. Fiziol., 2013, vol. 49, no. 1, p. 78.

    PubMed  CAS  Google Scholar 

  24. Smith, S.M., Vaughan, J.M., Donaldson, C.J., Rivier, J., Li, C., Chen, A., and Vale, W.W., Cocaine- and amphetamine-regulated transcript activates the hypothalamic-pituitary-adrenal axis through a corticotropin-releasing factor receptor-dependent mechanism, J. Endocrinology, 2004, vol. 145, no. 11, p. 5202.

    Article  CAS  Google Scholar 

  25. Stanley, S.A., Murphy, K.G., Bewick, G.A., Kong, W.M., Opacka-Juffry, J., Gardiner, J.V., Ghatei, M., Small, S.G., and Bloom, S.R., Regulation of rat pituitary cocaine- and amphetamine-regulated transcript (CART) by CRH and glucocorticoids, Am. J. Physiol. Endocrinol. Metab., 2004, vol. 287, no. 3, p. E583.

    Article  PubMed  CAS  Google Scholar 

  26. Bazhan, N.M., Makarova, E.N., Shevchenko, A.Yu., and Yakovleva, T.V., Repeated emotional stress obstacles the development of melanocortin-related obesity and type-2 diabetes in Agouti yellow-mutant mice, Ros. Fiziol. Zh. im. I.M. Sechenova, 2007, vol. 93, no. 11, p. 560.

    Google Scholar 

  27. Romanova, I.V., Chesnokova, A.Yu., and Mikhrina, A.L., Immunohistochemical study on CART-peptide in the striatonigral projections under dopamine-deficient conditions, Ros. Fiziol. Zh. im. I.M. Sechenova, 2012, vol. 98, no. 8, p. 980.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, 194223, Russia

    I. V. Romanova & A. L. Mikhrina

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  1. I. V. Romanova
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  2. A. L. Mikhrina
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Original Russian Text © I.V. Romanova, A.L. Mikhrina, 2013, published in Fiziologiya Cheloveka, 2013, Vol. 39, No. 6, pp. 24–30.

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Romanova, I.V., Mikhrina, A.L. Participation of agouti-related peptide in the regulation of the wakefulness-sleep cycle. Hum Physiol 39, 584–589 (2013). https://doi.org/10.1134/S0362119713060108

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