Neurochemical Journal

, Volume 12, Issue 1, pp 15–22 | Cite as

A Neurochemical Approach to the Search for Drugs for the Treatment of Symptoms of Alzheimer’s Disease

  • I. G. Sil’kis
Theoretical Articles


We performed an analysis of the reciprocal influences of neurons involved in the rapid-eye-movement phase of sleep (REM sleep) under the conditions of changes in the concentrations of various neuromodulators that are characteristic of Alzheimer’s disease. Several approaches to the search for drugs for the weakening of disease symptoms have been proposed taking the results of this analysis into account. The antagonists of orexin receptors were recently suggested for the treatment of Alzheimer’s disease because the anomalously high concentration of orexin, which is specific for this pathology, results in impairment of REM sleep. However, our analysis shows that the treatment with the antagonists of orexin receptors is not appropriate because it may lead to depression of the excitation of cholinergic cells, an additional decrease in the cholinergic deficit, and aggravation of symptoms of the disease. For the same reason it is unlikely that one should apply the antagonists of histamine H1 receptors and the agonists of adenosine A1 receptors. Substances that can lead to reduced activity of orexinergic neurons may be helpful instead. These substances include melatonin and the agonists of melatonin M1 receptors. Administration of these substances should improve REM sleep because it decreases the efficacy of excitation of orexinergic and histaminergic cells. Melanin-concentrating hormone also should decrease the efficacy of excitation of orexinergic cells. Additionally, the antagonists of histamine H3 receptors may be used because they promote the increased efficacy of excitation of neurons that secrete the melanin-concentrating hormone. Experimental evidence exists that indicates the benefits of these substances for improvement of REM sleep and attenuation of cognitive impairments in Alzheimer’s disease. These drugs must be applied before nightfall and their action should not be prolonged because orexinergic cells must be active in the daytime.


Alzheimer’s disease REM sleep modulation of synaptic transmission orexin melatonin melanin- concentrating hormone histamine 



Alzheimer’s disease


laterodorsal tegmental nucleus


melanin-concentrating hormone


MCH expressing neurons


melatonin sensitive receptors


pedunculopontine nucleus


orexinergic neurons


orexin-sensitive receptors

REM sleep

rapid eye movement or paradoxical sleep


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Liguori, C., Curr. Top. Behav. Neurosci., 2017, vol. 33, pp. 305–322.CrossRefPubMedGoogle Scholar
  2. 2.
    Gabelle, A., Jaussent, I., Hirtz, C., Vialaret, J., Navucet, S., Grasselli, C., Robert, P., Lehmann, S., and Dauvilliers, Y., Neurobiol. Aging, 2017, vol. 53, pp. 59–66.CrossRefPubMedGoogle Scholar
  3. 3.
    Liguori, C., Romigi, A., Nuccetelli, M., Zannino, S., Sancesario, G., Martorana, A., Albanese, M., Mercuri, N.B., Izzi, F., Bernardini, S., Nitti, A., Sancesario, G.M., Sica, F., Marciani, M.G., and Placidi, F., JAMA Neurol., 2014, vol. 71, no. 12, pp. 1498–1505.CrossRefPubMedGoogle Scholar
  4. 4.
    Malkki, H., Nat. Rev. Neurol., 2014, vol. 10, no. 12, p.672.CrossRefPubMedGoogle Scholar
  5. 5.
    Davies, J., Chen, J., Pink, R., Carter, D., Saunders, N., Sotiriadis, G., Bai, B., Pan, Y., Howlett, D., Payne, A., Randeva, H., and Karteris, E., Sci. Rep., vol. 5, p. 12584.Google Scholar
  6. 6.
    Osorio, R.S., Ducca, E.L., Wohlleber, M.E., Tanzi, E.B., Gumb, T., Twumasi, A., Tweardy, S., Lewis, C., Fischer, E., Koushyk, V., Cuartero-Toledo, M., Sheikh, M.O., Pirraglia, E., Zetterberg, H., Blennow, K., Lu, S.E., Mosconi, L., Glodzik, L., Schuetz, S., Varga, A.W., Ayappa, I., Rapoport, D.M., and de Leon, M.J., Sleep, 2016, vol. 39, no. 6, pp. 1253–1260.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cooke, J.R., Liu, L., Natarajan, L., He, F., Marler, M., Loredo, J.S., Corey-Bloom, J., Palmer, B.W., Greenfield, D., and Ancoli-Israel, S., Behav. Sleep Med., 2006, vol. 4, no. 4, pp. 219–227.CrossRefPubMedGoogle Scholar
  8. 8.
    Liguori, C., Nuccetelli, M., Izzi, F., Sancesario, G., Romigi, A., Martorana, A., Amoroso, C., Bernardini, S., Marciani, M.G., Mercuri, N.B., and Placidi, F., Neurobiol. Aging, 2016, vol. 40, pp. 120–126.CrossRefPubMedGoogle Scholar
  9. 9.
    Savaskan, E., Z. Gerontol. Geriatr., 2015, vol. 48, no. 4, pp. 312–317.CrossRefPubMedGoogle Scholar
  10. 10.
    Vecchierini, M.F., Psychol. Neuropsychiatr. Vieil., 2010, vol. 8, no. 1, pp. 15–23.PubMedGoogle Scholar
  11. 11.
    Busche, M.A., Kekus, M., and Forstl, H., Nervenarzt, 2017, vol. 88, no. 3, pp. 215–221.CrossRefPubMedGoogle Scholar
  12. 12.
    Slats, D., Claassen, J.A., Verbeek, M.M., and Overeem, S., Ageing Res. Rev., 2013, vol. 12, no. 1, pp. 188–200.CrossRefPubMedGoogle Scholar
  13. 13.
    Urrestarazu, E. and Iriarte, J., Nat. Sci. Sleep, 2016, vol. 8, pp. 21–33.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhang, B., Veasey, S.C., Wood, M.A., Leng, L.Z., Kaminski, C., Leight, S., Abel, T., Lee, V.M., and Trojanowski, J.Q., Am. J. Pathol., 2005, vol. 167, no. 5, pp. 1361–1369.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Shan, L., Dauvilliers, Y., and Siegel, J.M., Nat. Rev. Neurol., 2015, vol. 11, no. 7, pp. 401–413.CrossRefPubMedGoogle Scholar
  16. 16.
    Zlomuzica, A., Dere, D., Binder, S., De Souza Silva, M.A., Huston, J.P., and Dere, E., Neuropharmacology, 2016, vol. 106, pp. 135–145.CrossRefPubMedGoogle Scholar
  17. 17.
    Boyce, R., Glasgow, S.D., Williams, S., and Adamantidis, A., Science, 2016, vol. 352, no. 6287, pp. 812–826.CrossRefPubMedGoogle Scholar
  18. 18.
    Sil’kis, I.G., Neurochem. J., 2007, vol. 1, no. 1, pp. 21–30.CrossRefGoogle Scholar
  19. 19.
    Sil’kis, I.G., Neurochem. J., 2017, vol. 11, no. 2, pp. 138–148.CrossRefGoogle Scholar
  20. 20.
    Sil’kis, I.G., Zhurn. Vyssh. Nerv. Deyat. im. I.P. Pavlova, 2002, vol. 52, no. 4, pp. 392–405.Google Scholar
  21. 21.
    Ransmayr, G., Faucheux, B., Nowakowski, C., Kubis, N., Federspiel, S., Kaufmann, W., Henin, D., Hauw, J.J., Agid, Y., and Hirsch, E.C., Neurosci. Lett., 2000, vol. 288, no. 3, pp. 195–198.CrossRefPubMedGoogle Scholar
  22. 22.
    Wisor, J.P., Edgar, D.M., Yesavage, J., Ryan, H.S., McCormick, C.M., Lapustea, N., and Murphy, G.M., Jr., Neuroscience, 2005, vol. 131, no. 2, pp. 375–385.CrossRefPubMedGoogle Scholar
  23. 23.
    Hong, E.Y. and Lee, H.S., Brain Res., 2011, vol. 1383, pp. 169–78.CrossRefPubMedGoogle Scholar
  24. 24.
    Hong, E.Y., Yoon, Y.S., and Lee, H.S., Brain Res., 2011, vol. 1424, pp. 20–31.CrossRefPubMedGoogle Scholar
  25. 25.
    Papp, R.S. and Palkovits, M., Front. Neuroanat., 2014, vol. 8:34.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Burlet, S., Tyler, C.J., and Leonard, C.S., J. Neurosci., 2002, vol. 22, no. 7, pp. 2862–2872.CrossRefPubMedGoogle Scholar
  27. 27.
    Takahashi, K., Koyama, Y., Kayama, Y., and Yamamoto, M., Psychiatry Clin. Neurosci., 2002, vol. 56, no. 3, pp. 335–336.CrossRefPubMedGoogle Scholar
  28. 28.
    Arrigoni, E.L., Mochizuki, T., and Scammell, T.E., Acta Physiol. (Oxf.), 2010, vol. 198, no. 3, pp. 223–235.CrossRefGoogle Scholar
  29. 29.
    Fadel, J., Pasumarthi, R., and Reznikov, L.R., Neuroscience, 2005, vol. 130, no. 2, pp. 541–547.CrossRefPubMedGoogle Scholar
  30. 30.
    Bayer, L., Eggermann, E., Serafin, M., Grivel, J., Machard, D., Muhlethaler, M., and Jones, B.E., Neuroscience, 2005, vol. 130, no. 4, pp. 807–811.CrossRefPubMedGoogle Scholar
  31. 31.
    Yeomans, J.S., Handb. Exp. Pharmacol., 2012, vol. 208, pp. 243–259.CrossRefGoogle Scholar
  32. 32.
    García, A.P., Aitta-Aho, T., Schaaf, L., Heeley, N., Heuschmid, L., and Bai, Y.V., PLoS One, 2015, vol. 10, no. 8, e0133327.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Huang, Z.L., Qu, W.M., Li, W.D., Mochizuki, T., Eguchi, N., Watanabe, T., Urade, Y., and Hayaishi, O., Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, no. 17, pp. 9965–9970.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Khateb, A., Serafin, M., and Muhlethaler, M., Neurosci. Lett., 1990, vol. 112, nos. 2–3, pp. 257–262.CrossRefPubMedGoogle Scholar
  35. 35.
    Altinbas, B., Yilmaz, M.S., Savci, V., Jochem, J., and Yalcin, M., Auton. Neurosci., 2015, vol. 187, pp. 63–69.CrossRefPubMedGoogle Scholar
  36. 36.
    Zisapel, N., Expert. Opin. Emerg. Drugs, 2012, vol. 17, no. 3, pp. 299–317.CrossRefPubMedGoogle Scholar
  37. 37.
    Apergis-Schoute, J., Iordanidou, P., Faure, C., Jego, S., Schone, C., Aitta-Aho, T., Adamantidis, A., and Burdakov, D., J. Neurosci., 2015, vol. 35, no. 14, pp. 5435–5441.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Karnani, M.M., Szabó, G., Erdélyi, F., and Burdakov, D., J. Physiol., 2013, vol. 591, no. 4, pp. 933–953.CrossRefPubMedGoogle Scholar
  39. 39.
    Alam, M.N., Kumar, S., Bashir, T., Suntsova, N., Methippara, M.M., Szymusiak, R., and McGinty, D., J. Physiol., 2005, vol. 563, Pt. 2. pp. 569–582.CrossRefPubMedGoogle Scholar
  40. 40.
    Venner, A., Anaclet, C., Broadhurst, R.Y., Saper, C.B., and Fuller, P.M., Curr. Biol., vol. 26, no. 16, pp. 2137–2143.Google Scholar
  41. 41.
    Rao, Y., Lu, M., Ge, F., Marsh, D.J., Qian, S., Wang, A.H., Picciotto, M.R., and Gao, X.B., J. Neurosci., 2008, vol. 28, no. 37, pp. 9101–9110.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Gao, X.B. and Pol, A.N., J. Physiol., 2001, vol. 533, pt. 1, pp. 9101–9110.CrossRefGoogle Scholar
  43. 43.
    Yamashita, T. and Yamanaka, A., Curr. Opin. Neurobiol., 2017, vol. 44, pp. 94–100.CrossRefPubMedGoogle Scholar
  44. 44.
    Clément, O., Sapin, E., Libourel, P.A., Arthaud, S., Brischoux, F., Fort, P., and Luppi, P.H., J. Neurosci., 2012, vol. 32, no. 47, pp. 16763–16774.CrossRefPubMedGoogle Scholar
  45. 45.
    Parks, G.S., Olivas, N.D., Ikrar, T., Sanathara, N.M., Wang, L., Wang, Z., Civelli, O., and Xu, X., J. Physiol., 2014, vol. 592, no. 10, pp. 2183–2196.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Monti, J.M., Jantos, H., Boussard, M., Altier, H., Orellana, C., and Olivera, S., Eur. J. Pharmacol., 1991, vol. 205, no. 3, pp. 283–287.Google Scholar
  47. 47.
    Ishii, H., Tanaka, N., Kobayashi, M., Kato, M., and Sakuma, Y., J. Physiol. Sci., 2009, vol. 59, no. 1, pp. 37–47.CrossRefPubMedGoogle Scholar
  48. 48.
    Ng, K.Y., Leong, M.K., Liang, H., and Paxinos, G., Brain. Struct. Funct., 2017, vol. 222, no. 7, pp. 2921–2939.CrossRefPubMedGoogle Scholar
  49. 49.
    Wu, Y.H., Zhou, J.N., Balesar, R., Unmehopa, U., Bao, A., Jockers, R., Van Heerikhuize, J., and Swaab, D.F., J. Comp. Neurol., 2006, vol. 499, no. 6, pp. 897–910.CrossRefPubMedGoogle Scholar
  50. 50.
    Ramos, E., Egea, J., de Los, Rios, C., Marco-Contelles, J., and Romero, A., Future Med. Chem., 2017, vol. 9, no. 8, pp. 765–780.CrossRefPubMedGoogle Scholar
  51. 51.
    Cardinali, D.P., Brusco, L., Liberczuk, C., and Furio, A.M., Neuro Endocrinol. Lett., 2002, suppl. 1, pp. 20–23.Google Scholar
  52. 52.
    Sánchez-Barceló, E.J., Rueda, N., Mediavilla, M.D., Martínez-Cué, C., and Reiter, R.J., Curr. Med. Chem., 2017, vol. 24, no. 35, pp. 3851–3878.CrossRefPubMedGoogle Scholar
  53. 53.
    Zuev, V.A., Trifonov, N.I., Linkova, N.S., and Kvetnaia, T.V., Adv. Gerontol., 2017, vol. 30, no. 1, pp. 62–69.PubMedGoogle Scholar
  54. 54.
    Mishima, K., Tozawa, T., Satoh, K., Matsumoto, Y., Hishikawa, Y., and Okawa, M., Biol. Psychiatry, 1999, vol. 45, no. 4, pp. 417–421.CrossRefPubMedGoogle Scholar
  55. 55.
    Wu, Y.H. and Swaab, D.F., J. Pineal. Res., 2005, vol. 38, no. 3, pp. 145–152.CrossRefPubMedGoogle Scholar
  56. 56.
    Shukla, M., Boontem, P., Reiter, R.J., Satayavivad, J., and Govitrapong, P., Curr. Neuropharmacol., 2017, vol. 15, no. 7, pp. 1010–1031.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Zhou, J.N., Liu, R.Y., Kamphorst, W., Hofman, M.A., and Swaab, D.F., J. Pineal Res., 2003, vol. 35, no. 2, pp. 125–130.CrossRefPubMedGoogle Scholar
  58. 58.
    Brunner, P., Sözer-Topcular, N., Jockers, R., Ravid, R., Angeloni, D., Fraschini, F., Eckert, A., Müller-Spahn, F., and Savaskan, E., Eur. J. Histochem., 2006, vol. 50, no. 4, pp. 311–316.PubMedGoogle Scholar
  59. 59.
    Wu, Y.H., Ursinus, J., Zhou, J.N., Scheer, F.A., Ai-Min, B., Jockers, R., van Heerikhuize, J., and Swaab, D.F., J. Affect. Disord., 2013, vol. 148, nos. 2–3, pp. 357–367.CrossRefPubMedGoogle Scholar
  60. 60.
    Lacoste, B., Angeloni, D., Dominguez-Lopez, S., Calderoni, S., Mauro, A., Fraschini, F., Descarries, L., and Gobbi, G., J. Pineal. Res., 2015, vol. 58, no. 4, pp. 397–417.CrossRefPubMedGoogle Scholar
  61. 61.
    Schuster, C., J. Soc. Biol., 2007, vol. 201, no. 1, pp. 85–96.CrossRefPubMedGoogle Scholar
  62. 62.
    von Gall, C., Stehle, J.H., and Weaver, D.R., Cell Tissue Res., 2002, vol. 309, no. 1, pp. 151–162.CrossRefGoogle Scholar
  63. 63.
    Lax, P., J. Pineal. Res., 2008, vol. 44, pp. 70–77.PubMedGoogle Scholar
  64. 64.
    Schaefer, C., Kunz, D., and Bes, F., Curr. Alzheimer Res., 2017, vol. 14, no. 10, pp. 1084–1089.CrossRefPubMedGoogle Scholar
  65. 65.
    Comai, S., Ochoa-Sanchez, R., and Gobbi, G., Behav. Brain Res., 2013, vol. 243, pp. 231–238.CrossRefPubMedGoogle Scholar
  66. 66.
    Markus, R.P., Silva, C.L., Franco, D.G., Barbosa, E.M., Jr., and Ferreira, Z.S., Pharmacol. Ther., 2010, vol. 126, no. 3, pp. 251–262.CrossRefPubMedGoogle Scholar
  67. 67.
    Ozcan, M., Yilmaz, B., and Carpenter, D.O., Brain Res., 2006, vol. 1111, no. 1, pp. 90–94.CrossRefPubMedGoogle Scholar
  68. 68.
    Wang, L.M., Suthana, N.A., Chaudhury, D., Weaver, D.R., and Colwell, C.S., Eur. J. Neurosci., 2005, vol. 22, no. 9, pp. 2231–2237.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Sil’kis, I.G., Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 2008, vol. 58, no. 3, pp. 261–275.Google Scholar
  70. 70.
    Lazarus, M., Chen, J.F., Huang, Z.L., Urade, Y., and Fredholm, B.B., Handb. Exp. Pharmacol., 2017, [Epub ahead of print].Google Scholar
  71. 71.
    Marks, G.A., Birabil, C.G., and Speciale, S.G., Brain Res., 2005, vol. 1061, no. 2, pp. 124–127.CrossRefPubMedGoogle Scholar
  72. 72.
    Liu, Z.W. and Gao, X.B., J. Neurophysiol., 2007, vol. 97, no. 1, pp. 837–848.CrossRefPubMedGoogle Scholar
  73. 73.
    Alam, M.N., Kumar, S., Rai, S., Methippara, M., Szymusiak, R., and McGinty, D., Brain Res., 2009, vol. 1304, pp. 96–104.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Rai, S., Kumar, S., Alam, M.A., Szymusiak, R., McGinty, D., and Alam, M.N., Neuroscience, 2010, vol. 167, no. 1, pp. 40–48.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Oishi, Y., Huang, Z.L., Fredholm, B.B., Urade, Y., and Hayaishi, O., Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, no. 50, pp. 19992–19997.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    John, J., Kodama, T., and Siegel, J.M., Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014, vol. 307, no. 6, pp. R704–R710.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Strecker, R.E., Morairty, S., Thakkar, M.M., Porkka-Heiskanen, T., Basheer, R., Dauphin, L.J., Rainnie, D.G., Portas, C.M., Greene, R.W., and McCarley, R.W., Behav. Brain Res., 2000, vol. 115, no. 2, pp. 183–204.CrossRefPubMedGoogle Scholar
  78. 78.
    Yan, R., Hu, Z.Y., Zhou, W.X., Wang, Q., and Zhang, Y.X., Yao Xue Xue Bao, 2014, vol. 49, no. 6, pp. 751–756.PubMedGoogle Scholar
  79. 79.
    Vollert, C., Forkuo, G.S., Bond, R.A., and Eriksen, J.L., Neurosci. Lett., 2013, vol. 548, pp. 296–300.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Giunta, S., Andriolo, V., and Castorina, A., Int. J. Biochem. Cell. Biol., 2014, vol. 54, pp. 122–136.CrossRefPubMedGoogle Scholar
  81. 81.
    Kolahdouzan, M. and Hamadeh, M.J., CNS Neurosci. Ther., 2017, vol. 23, no. 4, pp. 272–290.CrossRefPubMedGoogle Scholar
  82. 82.
    Sil’kis, I.G., Ros. Fiziol. Zhurn. im. I.M. Sechenova, 2001, vol. 87, no. 2, pp. 155–169.Google Scholar
  83. 83.
    Florio, T., Scarnati, E., Confalone, G., Minchella, D., Galati, S., Stanzione, P., Stefani, A., and Mazzone, P., Eur. J. Neurosci., 2007, vol. 25, no. 4, pp. 1174–1186.CrossRefPubMedGoogle Scholar
  84. 84.
    Wang, Y.Y., Zheng, W., Ng, C.H., Ungvari, G.S., Wei, W., and Xiang, Y.T., Int. J. Geriatr. Psychiatry, 2017, vol. 32, no. 1, pp. 50–57.CrossRefPubMedGoogle Scholar
  85. 85.
    Peyron, C., Sapin, E., Leger, L., Luppi, P.H., and Fort, P., Peptides, 2009, vol. 30, no. 11, pp. 2052–2059.CrossRefPubMedGoogle Scholar
  86. 86.
    Verret, L., Goutagny, R., Fort, P., Cagnon, L., Salvert, D., Leger, L., Boissard, R., Salin, P., Peyron, C., and Luppi, P.H., BMC Neurosci., 2003, vol. 4, p.19.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Adamantidis, A. and de Lecea, L., Peptides, 2009, vol. 30, no. 11, pp. 2066–2070.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Schmidt, F.M., Kratzsch, J., Gertz, H.J., Tittmann, M., Jahn, I., Pietsch, U.C., Kaisers, U.X., Thiery, J., Hegerl, U., and Schönknecht, P., PLoS One, 2013, vol. 8, no. 5, e63136.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Naddafi, F. and Mirshafiey, A., Am. J. Alzheimers Dis. Other Dement., 2013, vol. 28, no. 4, pp. 327–336.CrossRefGoogle Scholar
  90. 90.
    Sadek, B., Saad, A., Sadeq, A., Jalal, F., and Stark, H., Behav. Brain Res., 2016, vol. 312, pp. 415–430.CrossRefPubMedGoogle Scholar
  91. 91.
    Vohora, D. and Bhowmik, M., Front. Syst. Neurosci., 2012, vol. 6, p.72.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Fang, J., Li, Y., Liu, R., Pang, X., Li, C., Yang, R., He, Y., Lian, W., Liu, A.L., and Du, G.H., J. Chem. Inf. Model, 2015, vol. 55, no. 1, pp. 149–164.CrossRefPubMedGoogle Scholar
  93. 93.
    Grove, R.A., Harrington, C.M., Mahler, A., Beresford, I., Maruff, P., Lowy, M.T., Nicholls, A.P., Boardley, R.L., Berges, A.C., Nathan, P.J., and Horrigan, J.P., Curr. Alzheimer’s Res., 2014, vol. 11, no. 1, pp. 47–58.CrossRefGoogle Scholar
  94. 94.
    Nathan, P.J., Boardley, R., Scott, N., Berges, A., Maruff, P., Sivananthan, T., Upton, N., Lowy, M.T., Nestor, P.J., and Lai, R., Curr. Alzheimer’s Res., 2013, vol. 10, no. 3, pp. 240–251.CrossRefGoogle Scholar
  95. 95.
    Schlicker, E. and Kathmann, M., Handb. Exp. Pharmacol., 2017, vol. 241, pp. 277–299.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Institute of Higher Nervous Activity and NeurophysiologyRussian Academy of SciencesMoscowRussia
  2. 2.MoscowRussia

Personalised recommendations