A Neurochemical Approach to the Search for Drugs for the Treatment of Symptoms of Alzheimer’s Disease
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Abstract
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.
Keywords
Alzheimer’s disease REM sleep modulation of synaptic transmission orexin melatonin melanin- concentrating hormone histamineAbbreviation
- AD
Alzheimer’s disease
- LDTN
laterodorsal tegmental nucleus
- MCH
melanin-concentrating hormone
- MCHNs
MCH expressing neurons
- MT1
melatonin sensitive receptors
- PPN
pedunculopontine nucleus
- ORNs
orexinergic neurons
- ORX
orexin-sensitive receptors
- REM sleep
rapid eye movement or paradoxical sleep
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- 1.Liguori, C., Curr. Top. Behav. Neurosci., 2017, vol. 33, pp. 305–322.CrossRefPubMedGoogle Scholar
- 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.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.Malkki, H., Nat. Rev. Neurol., 2014, vol. 10, no. 12, p.672.CrossRefPubMedGoogle Scholar
- 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.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.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.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.Savaskan, E., Z. Gerontol. Geriatr., 2015, vol. 48, no. 4, pp. 312–317.CrossRefPubMedGoogle Scholar
- 10.Vecchierini, M.F., Psychol. Neuropsychiatr. Vieil., 2010, vol. 8, no. 1, pp. 15–23.PubMedGoogle Scholar
- 11.Busche, M.A., Kekus, M., and Forstl, H., Nervenarzt, 2017, vol. 88, no. 3, pp. 215–221.CrossRefPubMedGoogle Scholar
- 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.Urrestarazu, E. and Iriarte, J., Nat. Sci. Sleep, 2016, vol. 8, pp. 21–33.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.Shan, L., Dauvilliers, Y., and Siegel, J.M., Nat. Rev. Neurol., 2015, vol. 11, no. 7, pp. 401–413.CrossRefPubMedGoogle Scholar
- 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.Boyce, R., Glasgow, S.D., Williams, S., and Adamantidis, A., Science, 2016, vol. 352, no. 6287, pp. 812–826.CrossRefPubMedGoogle Scholar
- 18.Sil’kis, I.G., Neurochem. J., 2007, vol. 1, no. 1, pp. 21–30.CrossRefGoogle Scholar
- 19.Sil’kis, I.G., Neurochem. J., 2017, vol. 11, no. 2, pp. 138–148.CrossRefGoogle Scholar
- 20.Sil’kis, I.G., Zhurn. Vyssh. Nerv. Deyat. im. I.P. Pavlova, 2002, vol. 52, no. 4, pp. 392–405.Google Scholar
- 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.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.Hong, E.Y. and Lee, H.S., Brain Res., 2011, vol. 1383, pp. 169–78.CrossRefPubMedGoogle Scholar
- 24.Hong, E.Y., Yoon, Y.S., and Lee, H.S., Brain Res., 2011, vol. 1424, pp. 20–31.CrossRefPubMedGoogle Scholar
- 25.Papp, R.S. and Palkovits, M., Front. Neuroanat., 2014, vol. 8:34.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Burlet, S., Tyler, C.J., and Leonard, C.S., J. Neurosci., 2002, vol. 22, no. 7, pp. 2862–2872.PubMedGoogle Scholar
- 27.Takahashi, K., Koyama, Y., Kayama, Y., and Yamamoto, M., Psychiatry Clin. Neurosci., 2002, vol. 56, no. 3, pp. 335–336.CrossRefPubMedGoogle Scholar
- 28.Arrigoni, E.L., Mochizuki, T., and Scammell, T.E., Acta Physiol. (Oxf.), 2010, vol. 198, no. 3, pp. 223–235.CrossRefGoogle Scholar
- 29.Fadel, J., Pasumarthi, R., and Reznikov, L.R., Neuroscience, 2005, vol. 130, no. 2, pp. 541–547.CrossRefPubMedGoogle Scholar
- 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.Yeomans, J.S., Handb. Exp. Pharmacol., 2012, vol. 208, pp. 243–259.CrossRefGoogle Scholar
- 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.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.Khateb, A., Serafin, M., and Muhlethaler, M., Neurosci. Lett., 1990, vol. 112, nos. 2–3, pp. 257–262.CrossRefPubMedGoogle Scholar
- 35.Altinbas, B., Yilmaz, M.S., Savci, V., Jochem, J., and Yalcin, M., Auton. Neurosci., 2015, vol. 187, pp. 63–69.CrossRefPubMedGoogle Scholar
- 36.Zisapel, N., Expert. Opin. Emerg. Drugs, 2012, vol. 17, no. 3, pp. 299–317.CrossRefPubMedGoogle Scholar
- 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.Karnani, M.M., Szabó, G., Erdélyi, F., and Burdakov, D., J. Physiol., 2013, vol. 591, no. 4, pp. 933–953.CrossRefPubMedGoogle Scholar
- 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.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.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.Gao, X.B. and Pol, A.N., J. Physiol., 2001, vol. 533, pt. 1, pp. 9101–9110.CrossRefGoogle Scholar
- 43.Yamashita, T. and Yamanaka, A., Curr. Opin. Neurobiol., 2017, vol. 44, pp. 94–100.CrossRefPubMedGoogle Scholar
- 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.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.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.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.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.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.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.Cardinali, D.P., Brusco, L., Liberczuk, C., and Furio, A.M., Neuro Endocrinol. Lett., 2002, suppl. 1, pp. 20–23.Google Scholar
- 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.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.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.Wu, Y.H. and Swaab, D.F., J. Pineal. Res., 2005, vol. 38, no. 3, pp. 145–152.CrossRefPubMedGoogle Scholar
- 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.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.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.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.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.Schuster, C., J. Soc. Biol., 2007, vol. 201, no. 1, pp. 85–96.CrossRefPubMedGoogle Scholar
- 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.Lax, P., J. Pineal. Res., 2008, vol. 44, pp. 70–77.PubMedGoogle Scholar
- 64.Schaefer, C., Kunz, D., and Bes, F., Curr. Alzheimer Res., 2017, vol. 14, no. 10, pp. 1084–1089.CrossRefPubMedGoogle Scholar
- 65.Comai, S., Ochoa-Sanchez, R., and Gobbi, G., Behav. Brain Res., 2013, vol. 243, pp. 231–238.CrossRefPubMedGoogle Scholar
- 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.Ozcan, M., Yilmaz, B., and Carpenter, D.O., Brain Res., 2006, vol. 1111, no. 1, pp. 90–94.CrossRefPubMedGoogle Scholar
- 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.Sil’kis, I.G., Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 2008, vol. 58, no. 3, pp. 261–275.Google Scholar
- 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.Marks, G.A., Birabil, C.G., and Speciale, S.G., Brain Res., 2005, vol. 1061, no. 2, pp. 124–127.CrossRefPubMedGoogle Scholar
- 72.Liu, Z.W. and Gao, X.B., J. Neurophysiol., 2007, vol. 97, no. 1, pp. 837–848.CrossRefPubMedGoogle Scholar
- 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.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.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.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.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.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.Vollert, C., Forkuo, G.S., Bond, R.A., and Eriksen, J.L., Neurosci. Lett., 2013, vol. 548, pp. 296–300.CrossRefPubMedPubMedCentralGoogle Scholar
- 80.Giunta, S., Andriolo, V., and Castorina, A., Int. J. Biochem. Cell. Biol., 2014, vol. 54, pp. 122–136.CrossRefPubMedGoogle Scholar
- 81.Kolahdouzan, M. and Hamadeh, M.J., CNS Neurosci. Ther., 2017, vol. 23, no. 4, pp. 272–290.CrossRefPubMedGoogle Scholar
- 82.Sil’kis, I.G., Ros. Fiziol. Zhurn. im. I.M. Sechenova, 2001, vol. 87, no. 2, pp. 155–169.Google Scholar
- 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.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.Peyron, C., Sapin, E., Leger, L., Luppi, P.H., and Fort, P., Peptides, 2009, vol. 30, no. 11, pp. 2052–2059.CrossRefPubMedGoogle Scholar
- 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.Adamantidis, A. and de Lecea, L., Peptides, 2009, vol. 30, no. 11, pp. 2066–2070.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.Naddafi, F. and Mirshafiey, A., Am. J. Alzheimers Dis. Other Dement., 2013, vol. 28, no. 4, pp. 327–336.CrossRefGoogle Scholar
- 90.Sadek, B., Saad, A., Sadeq, A., Jalal, F., and Stark, H., Behav. Brain Res., 2016, vol. 312, pp. 415–430.CrossRefPubMedGoogle Scholar
- 91.Vohora, D. and Bhowmik, M., Front. Syst. Neurosci., 2012, vol. 6, p.72.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.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.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.Schlicker, E. and Kathmann, M., Handb. Exp. Pharmacol., 2017, vol. 241, pp. 277–299.CrossRefPubMedGoogle Scholar