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Mechanisms of phototherapy of Alzheimer’s disease during sleep and wakefulness: the role of the meningeal lymphatics |
Semyachkina‑Glushkovskaya Oxana1,2( ), Shirokov Alexander2,3, Blokhina Inna2, Fedosov Ivan2, Terskov Andrey2, Dubrovsky Alexander2, Tsoy Maria2, Elovenko Daria2, Adushkina Viktoria2, Evsukova Arina2, Telnova Valeria2, Tzven Anna2, Krupnova Valeria2, Manzhaeva Maria2, Dmitrenko Alexander2, Penzel Thomas2,4, Kurths Jürgen1,2,5 |
1. Institute of Physics, Humboldt University, Berlin 12489, Germany
2. Department of Biology, Saratov State University, Saratov 410012, Russia
3. Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Saratov 410049, Russia
4. Charité – Universitätsmedizin Berlin, Berlin 10117, Germany
5. Department of Complexity Scienc, Potsdam Institute for Climate Impact Research, Potsdam 14473, Germany |
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Abstract With the increase in the aging population, the global number of people with Alzheimer’s disease (AD) progressively increased worldwide. The situation is aggravated by the fact that there is no the effective pharmacological therapy of AD. Photobiomodulation (PBM) is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies. However, the mechanisms of therapeutic effects of PBM for AD are poorly understood. In this study on mice, we demonstrate that photodynamic effects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels (MLVs) leading to suppression of lymphatic removal of beta-amyloid (Aβ) from the right lateral ventricle and the hippocampus. Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice, we discover that the 7-day course of PBM during deep sleep vs. wakefulness provides better restoration of clearance of Aβ from the ventricular system of the brain and the hippocampus. Our results shed light on the mechanism of PBM and show the stimulating effects of PBM on the brain lymphatic drainage that promotes transport of Aβ via the lymphatic pathway. The effects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.
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| Keywords
Alzheimer’s disease
Photobiomodulation
Brain lymphatics
Sleep
Mechanisms
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Corresponding Author(s):
Semyachkina‑Glushkovskaya Oxana
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| About author: Peng Lei and Charity Ngina Mwangi contributed equally to this work. |
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Issue Date: 26 October 2023
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X. Li,, X. Feng,, X. Sun,, N. Hou,, F. Han,, Y. Liu,: Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2019. Front. Aging Neurosci. 14, 937486 (2022)
https://doi.org/10.3389/fnagi.2022.937486
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C.J.L. Murray,, A.Y. Aravkin,, P. Zheng,, C. Abbafati,, K.M. Abbas,, M. Abbasi-Kangevari,, F. Abd-Allah,, A. Abdelalim,, M. Abdollahi,, I. Abdollahpour,, K.H. Abegaz,, H. Abolhassani,, V. Aboyans,, L.G. Abreu,, M.R.M. Abrigo,, A. Abualhasan,, L.J. Abu-Raddad,, A.I. Abushouk,, M. Adabi,, V. Adekanmbi,, A.M. Adeoye,, O.O. Adetokunboh,, D. Adham,, S.M. Advani,, G. Agarwal,, S.M.K. Aghamir,, A. Agrawal,, T. Ahmad,, K. Ahmadi,, M. Ahmadi,, H. Ahmadieh,, M.B. Ahmed,, T.Y. Akalu,, R.O. Akinyemi,, T. Akinyemiju,, B. Akombi,, C.J. Akunna,, F. Alahdab,, Z. Al-Aly,, K. Alam,, S. Alam,, T. Alam,, F.M. Alanezi,, T.M. Alanzi,, B. Alemu,, K.F. Alhabib,, M. Ali,, S. Ali,, G. Alicandro,, C. Alinia,, V. Alipour,, H. Alizade,, S.M. Aljunid,, F. Alla,, P. Allebeck,, A. Almasi-Hashiani,, H.M. Al-Mekhlafi,, J. Alonso,, K.A. Altirkawi,, M. Amini-Rarani,, F. Amiri,, D.A. Amugsi,, R. Ancuceanu,, D. Anderlini,, J.A. Anderson,, C.L. Andrei,, T. Andrei,, C. Angus,, M. Anjomshoa,, F. Ansari,, A. 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John,, Y.O. John-Akinola,, C.O. Johnson,, J.B. Jonas,, F. Joukar,, J.J. Jozwiak,, M. Jürisson,, A. Kabir,, Z. Kabir,, H. Kalani,, R. Kalani,, L.R. Kalankesh,, R. Kalhor,, T. Kanchan,, N. Kapoor,, B. Karami Matin,, A. Karch,, M.A. Karim,, G.M. Kassa,, S.V. Katikireddi,, G.A. Kayode,, A. Kazemi Karyani,, P.N. Keiyoro,, C. Keller,, L. Kemmer,, P.J. Kendrick,, N. Khalid,, M. Khammarnia,, E.A. Khan,, M. Khan,, K. Khatab,, M.M. Khater,, M.N. Khatib,, M. Khayamzadeh,, S. Khazaei,, C. Kieling,, Y.J. Kim,, R.W. Kimokoti,, A. Kisa,, S. Kisa,, M. Kivimäki,, L.D. Knibbs,, A.K.S. Knudsen,, J.M. Kocarnik,, S. Kochhar,, J.A. Kopec,, V.A. Korshunov,, P.A. Koul,, A. Koyanagi,, M.U.G. Kraemer,, K. Krishan,, K.J. Krohn,, H. Kromhout,, B. Kuate Defo,, G.A. Kumar,, V. Kumar,, O.P. Kurmi,, D. Kusuma,, C. La Vecchia,, B. Lacey,, D.K. Lal,, R. Lalloo,, T. Lallukka,, F.H. Lami,, I. Landires,, J.J. Lang,, S.M. Langan,, A.O. Larsson,, S. Lasrado,, P. Lauriola,, J.V. Lazarus,, P.H. Lee,, S.W.H. Lee,, K.E. 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