Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65170610.31857/S0869813923110067GUUNFAREVIEW AND PROBLEM ARTICLESОБЗОРНЫЕ И ПРОБЛЕМНЫЕ СТАТЬИModeling Taupathies in Zebrafish (Danio rerio)Моделирование таупатий на Danio rerioKotovaМ. М.КотоваМ. М.avkalueff@gmail.comKolesnikovaТ. О.КолесниковаТ. О.avkalueff@gmail.comKalueffA. V.КалуевА. В.avkalueff@gmail.comDivision of Neurobiology, Sirius University of Science and TechnologyНаучный центр генетики и наук о жизни, Научно-технологический университет “Сириус”Institute of Translational Biomedicine, St. Petersburg State UniversityИнститут трансляционной биомедицины, Санкт-Петербургский государственный университетUral Federal UniversityУральский федеральный университетAlmazov National Medical Research Center, Ministry of Healthcare of Russian FederationНациональный медицинский исследовательский центр им. В.А. Алмазова МЗ РФGranov Russian Research Center for Radiology and Surgical Technologies, Ministry of Healthcare of Russian FederationРоссийский научный центр радиологии и хирургических технологий им. акад. А.М. Гранова МЗ РФ01112023109111547156601022025Copyright ©; 2023, М.М. Котова, Т.О. Колесникова, А.В. КалуевCopyright ©; 2023, М.М. Котова, Т.О. Колесникова, А.В. Калуев2023М.М. Котова, Т.О. Колесникова, А.В. КалуевМ.М. Котова, Т.О. Колесникова, А.В. Калуевhttps://journals.eco-vector.com/0869-8139/article/view/651706

Taupathies are a group of neurodegenerative diseases characterized by the accumulation of tau-protein in the brain, causing clinical dementia. Tau protein stabilizes microtubules and regulates axonal transport, however, when hyper-phosphorylated, aggregates in the brain. Taupaties can be divided into primary and secondary (e.g., Alzheimer’s disease). Experimental animal models models are an important tool to study taupathies. Here, we discuss molecular mechanisms of taupathies and their existing experimental models in both rodents and novel alternative organisms, zebrafish (Danio rerio), as well as future novel directions of research in this field.

Таупатии – гетерогенная группа прогрессирующих нейродегенеративных заболеваний, вызванных накоплением в мозге агрегатов тау-белка. Тау-белок стабилизирует состояние микротубочек и регулирует аксональный транспорт, однако при гиперфосфорилировании начинает откладываться в мозге в виде агрегатов, являясь основным патогенетическим механизмом возникновения таупатий. По степени вовлеченности тау-белка в патогенез заболевания выделяют первичные и вторичные таупатии. Наиболее распространенной вторичной таупатией является болезнь Альцгеймера. Экспериментальные модели на животных являются важным методом исследования физиологии тау-белка и патогенеза таупатий. В работе обсуждаются современные представления о молекулярных механизмах таупатий, а также существующие экспериментальные модели таупатий на новых альтернативных модельных объектах – рыбах зебраданио (zebrafish, Danio rerio), и новые направления исследований в данной области.

Кeywords: zebrafishtaupathiesanimal modelneurodegenerationtau protein: зебраданиотаупатииживотные моделинейродегенерациятау-белокВасенина ЕЕ, Левин ОС (2020) Современные подходы к клинической диагностике и лечению мультисистемных дегенераций, связанных с накоплением тау-протеина. Журн неврол психиатр им СС Корсакова 120(10-2): 22–30. [Vasenina EE, Levin OS (2020) Contemporary approaches to clinical diagnosis and treatment of tau-protein accumulation related multisystem degenerations. Zh Nevrol Psikhiatr im SS Korsakova 120(10-2): 22–30 (In Russ)]. https://doi.org/10.17116/jnevro202012010222Kovacs GG (2017) Tauopathies. Handb Clin Neurol 145: 355–368. https://doi.org/10.1016/b978-0-12-802395-2.00025-0Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A 72(5): 1858–1862. https://doi.org/10.1073/pnas.72.5.1858Cleveland DW, Hwo SY, Kirschner MW (1977) Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly. J Mol Biol 116(2): 227–247. https://doi.org/10.1016/0022-2836(77)90214-5Kempf M, Clement A, Faissner A, Lee G, Brandt R (1996) Tau Binds to the Distal Axon Early in Development of Polarity in a Microtubule- and Microfilament-Dependent Manner. J Neurosci 16(18): 5583–5592. https://doi.org/10.1523/jneurosci.16-18-05583.1996Sotiropoulos I, Galas M-C, Silva JM, Skoulakis E, Wegmann S, Maina MB, Blum D, Sayas CL, Mandelkow E-M, Mandelkow E, Spillantini MG, Sousa N, Avila J, Medina M, Mudher A, Buee L (2017) Atypical, non-standard functions of the microtubule associated Tau protein. Acta Neuropathol Commun 5(1): 91. https://doi.org/10.1186/s40478-017-0489-6Papanikolopoulou K, Roussou IG, Gouzi JY, Samiotaki M, Panayotou G, Turin L, Skoulakis EMC (2019) Drosophila Tau Negatively Regulates Translation and Olfactory Long-Term Memory, But Facilitates Footshock Habituation and Cytoskeletal Homeostasis. J Neurosci 39(42): 8315–8329. https://doi.org/10.1523/jneurosci.0391-19.2019Evans HT, Taylor D, Kneynsberg A, Bodea L-G, Götz J (2021) Altered ribosomal function and protein synthesis caused by tau. Acta Neuropathol Commun (91): 110. https://doi.org/10.1186/s40478-021-01208-4Wegmann S, Biernat J, Mandelkow E (2021) A current view on Tau protein phosphorylation in Alzheimer’s disease. Curr Opinion Neurobiol 69: 131–138. https://doi.org/10.1016/j.conb.2021.03.003Pick’s Disease. Accessed 20 March 2023. https://my.clevelandclinic.org/health/diseases/22637-picks-disease# (2022)Swallow DMA, Zheng CS, Counsell CE (2022) Systematic Review of Prevalence Studies of Progressive Supranuclear Palsy and Corticobasal Syndrome. Mov Disord Clin Pract 9(5): 604–613. https://doi.org/10.1002/mdc3.13489Forrest SL, Kril JJ, Kovacs GG (2021) Association Between Globular Glial Tauopathies and Frontotemporal Dementia-Expanding the Spectrum of Gliocentric Disorders: A Review. JAMA Neurol 78(8): 1004–1014. https://doi.org/10.1001/jamaneurol.2021.1813Всемирная Организация Здравоохранения: Деменция (2019). Accessed 2023World Health Organization: Dementia.Sultan A, Nesslany F, Violet M, Bégard S, Loyens A, Talahari S, Mansuroglu Z, Marzin D, Sergeant N, Humez S, Colin M, Bonnefoy E, Buée L, Galas MC (2011) Nuclear tau, a key player in neuronal DNA protection. J Biol Chem 286(6): 4566–4575. https://doi.org/10.1074/jbc.M110.199976Wegmann S, Biernat J, Mandelkow E (2021) A current view on Tau protein phosphorylation in Alzheimer’s disease. Curr Opin Neurobiol 69: 131–138. https://doi.org/10.1016/j.conb.2021.03.003Tapia-Rojas C, Cabezas-Opazo F, Deaton CA, Vergara EH, Johnson GVW, Quintanilla RA (2019) It’s all about tau. Prog Neurobiol 175: 54–76. https://doi.org/10.1016/j.pneurobio.2018.12.005Mietelska-Porowska A, Wasik U, Goras M, Filipek A, Niewiadomska G (2014) Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci 15(3): 4671–4713. https://doi.org/10.3390/ijms15034671Hanger DP, Anderton BH, Noble W (2009) Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 15(3): 112–119. https://doi.org/10.1016/j.molmed.2009.01.003Pei JJ, Tanaka T, Tung YC, Braak E, Iqbal K, Grundke-Iqbal I (1997) Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain. J Neuropathol Exp Neurol 56(1): 70–78. https://doi.org/10.1097/00005072-199701000-00007Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402(6762): 615–622. https://doi.org/10.1038/45159Schwab C, DeMaggio AJ, Ghoshal N, Binder LI, Kuret J, McGeer PL (2000) Casein kinase 1 delta is associated with pathological accumulation of tau in several neurodegenerative diseases. Neurobiol Aging 21(4): 503–510. https://doi.org/10.1016/s0197-4580(00)00110-xFuster-Matanzo A, Hernández F, Ávila J (2018) Tau Spreading Mechanisms; Implications for Dysfunctional Tauopathies. Int J Mol Sci 19(3): 645. https://doi.org/10.3390/ijms19030645Merezhko M, Uronen R-L, Huttunen HJ (2020) The Cell Biology of Tau Secretion. Front Mol Neurosci 13: 569818. https://doi.org/10.3389/fnmol.2020.569818Pooler AM, Phillips EC, Lau DHW, Noble W, Hanger DP (2013) Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14(4): 389–394. https://doi.org/10.1038/embor.2013.15Cripps D, Thomas SN, Jeng Y, Yang F, Davies P, Yang AJ (2006) Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J Biol Chem 281(16): 10825–10838. https://doi.org/10.1074/jbc.M512786200Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64(2): 113–122. https://doi.org/10.1093/jnen/64.2.113Kovacs GG, Rozemuller AJM, van Swieten JC, Gelpi E, Majtenyi K, Al-Sarraj S, Troakes C, Bódi I, King A, Hortobágyi T, Esiri MM, Ansorge O, Giaccone G, Ferrer I, Arzberger T, Bogdanovic N, Nilsson T, Leisser I, Alafuzoff I, Ironside JW, Kretzschmar H, Budka H (2013) Neuropathology of the hippocampus in FTLD-Tau with Pick bodies: a study of the BrainNet Europe Consortium. Neuropathol Appl Neurobiol 39(2): 166–178. https://doi.org/10.1111/j.1365-2990.2012.01272.xWilliams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, Revesz T (2007) Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome. Brain 130(6): 1566–1576. https://doi.org/10.1093/brain/awm104Dickson DW, Rademakers R, Hutton ML (2007) Progressive Supranuclear Palsy: Pathology and Genetics. Brain Pathol 17(1): 74–82. https://doi.org/10.1111/j.1750-3639.2007.00054.xArima K (2006) Ultrastructural characteristics of tau filaments in tauopathies: Immuno-electron microscopic demonstration of tau filaments in tauopathies. Neuropathology 26(5): 475–483. https://doi.org/https://doi.org/10.1111/j.1440-1789.2006.00669.xVaquer-Alicea J, Diamond MI, Joachimiak LA (2021) Tau strains shape disease. Acta Neuropathol 142(1): 57–71. https://doi.org/10.1007/s00401-021-02301-7Kesika P, Suganthy N, Sivamaruthi BS, Chaiyasut C (2021) Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease. Life Sci 264: 118627. https://doi.org/10.1016/j.lfs.2020.118627Breijyeh Z, Karaman R (2020) Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules 25: 24. https://doi.org/10.3390/molecules25245789Armstrong RA (2019) Risk factors for Alzheimer’s disease. Folia Neuropathol 57(2): 87–105. https://doi.org/10.5114/fn.2019.85929Lamb R, Rohrer JD, Lees AJ, Morris HR (2016) Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options. Curr Treat Options Neurol 18(9): 42. https://doi.org/10.1007/s11940-016-0422-5Herrmann N, Black SE, Chow T, Cappell J, Tang-Wai DF, Lanctôt KL (2012) Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatry 20(9): 789–797. https://doi.org/10.1097/JGP.0b013e31823033f3Alam S, Lingenfelter KS, Bender AM, Lindsley CW (2017) Classics in Chemical Neuroscience: Memantine. ACS Chem Neurosci 8(9): 1823–1829. https://doi.org/10.1021/acschemneuro.7b00270Ni R, Chen Z, Gerez JA, Shi G, Zhou Q, Riek R, Nilsson KPR, Razansky D, Klohs J (2020) Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy. Biomed Opt Express 11(9): 4989–5002. https://doi.org/10.1364/boe.395803Belfiore R, Rodin A, Ferreira E, Velazquez R, Branca C, Caccamo A, Oddo S (2019) Temporal and regional progression of Alzheimer’s disease-like pathology in 3xTg-AD mice. Aging Cell 18(1): e12873. https://doi.org/10.1111/acel.12873Dey M, Singh RK (2022) Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer’s disease. Toxicol Mech Methods 32(8): 616–627. https://doi.org/10.1080/15376516.2022.2058898Tozlu Ö, Türkez H, Okkay U, Ceylan O, Bayram C, Hacımüftüoğlu A, Mardinoğlu A (2022) Assessment of the neuroprotective potential of d-cycloserine and l-serine in aluminum chloride-induced experimental models of Alzheimer’s disease: In vivo and in vitro studies. Front Nutr 9: 981889. https://doi.org/10.3389/fnut.2022.981889Lu Y, Dong Y, Tucker D, Wang R, Ahmed ME, Brann D, Zhang Q (2017) Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease. J Alzheimer’s Dis 56(4): 1469–1484. https://doi.org/10.3233/jad-160869Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Guerrero-Munoz MJ, Kiritoshi T, Neugebauer V, Jackson GR, Kayed R (2012) Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau. Sci Rep 2: 700. https://doi.org/10.1038/srep00700Moe JG, Chatterjee I, Puzzo D, Agnieszka S, Fa M, Davidowitz EJ, Arancio O (2010) P1-361: Extracellular oligomeric tau inhibits memory formation in mice. Alzheimers 6(4S)(Part9): S277. https://doi.org/10.1016/j.jalz.2010.05.915Gistelinck M, Lambert JC, Callaerts P, Dermaut B, Dourlen P (2012) Drosophila models of tauopathies: what have we learned? Int J Alzheimers Dis 2012: 970980. https://doi.org/10.1155/2012/970980Giong HK, Subramanian M, Yu K, Lee JS (2021) Non-Rodent Genetic Animal Models for Studying Tauopathy: Review of Drosophila, Zebrafish, and C. elegans Models. Int J Mol Sci 22: 16. https://doi.org/10.3390/ijms22168465Кротова НА, Лакстыгал АМ, Таранов АС, Ильин НП, Бытов МВ, Волгин АД, Амстиславская ТГ, Демин КА, Калуев АВ (2019) Зебраданио (zebrafish) как новая перспективная модель в трансляционной нейробиологии. Рос физиол журн им ИМ Сеченова 105: 1417–1435. [Krotova NA, Lakstygal AM, Taranov AS, Ilyin NP, Bytov MV, Volgin AD, Amstislavskaya TG, Demin KA, Kalueff AV (2019) Zebrafish as a promising new model in translational neurobiology. Russ J Physiol 105: 1417–1435. (In Russ)]. https://doi.org/10.1134/S0869813919110062Галстян ДС, Колесникова ТО, Косицын ЮМ, Забегалов КН, Губайдуллина МА, Маслов ГО, Демин КА, Калуев АВ (2022) Моделирование и оценка судорожной активности у зебраданио (Danio rerio). Обзоры клин фармакол лекарств терапии 20: 193–199. [Galstyan DS, Kolesnikova TO, Kositsyn YM, Zabegalov KN, Gubaidullina MA, Maslov GO, Demin KA, Kalueff AV (2022) Modeling and assaying seizure activity in zebrafish (Danio rerio). Rev Clin Pharmacol Drug Ther 20: 193–199. (In Russ)]. https://doi.org/10.17816/RCF202193-199Державина КА, Ильин НП, Серединская МВ, Неруш МО, Захарченко КВ, Сорокин ДВ, Демин КА, Калуев АВ (2022) Зебраданио (zebrafish) как модель редких (орфанных) заболеваний нервной системы. Рос журн персонал мед 2: 17–32. [Derzhavina KA, Ilyin NP, Seredinskaya MV, Nerush MO, Zakharchenko KV, Sorokin DV, Demin KA, Kalueff AV (2022) Zebrafish as a model organism for rare diseases of nervous system. Russ J Person Med 2: 17–32. (In Russ)]. https://doi.org/10.18705/2782-3806-2022-2-2-17-32Калуев АВ (2022) Принципы моделирования заболеваний мозга и их терапии на зебраданио (zebrafish). Обзоры клин фармакол лекарств терапии 20: 119–122. [Kalueff AV (2022) Principles of modeling brain diseases and their therapy based on zebrafish studies. Rev Clin Pharmacol Drug Ther 20: 119–122. (In Russ)]. https://doi.org/10.17816/RCF202119-122Horzmann KA, Freeman JL (2016) Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity. Toxics 4(3): 19. https://doi.org/10.3390/toxics4030019Wasel O, Freeman JL (2020) Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration. Int J Mol Sci 21(17): 5981. https://doi.org/10.3390/ijms21175981Roberts A, Bill B, Glanzman D (2013) Learning and memory in zebrafish larvae. Front Neural Circuits 7: 126. https://doi.org/10.3389/fncir.2013.00126Shenoy A, Banerjee M, Upadhya A, Bagwe-Parab S, Kaur G (2022) The Brilliance of the Zebrafish Model: Perception on Behavior and Alzheimer’s Disease. Front Behav Neurosci 16: 861155. https://doi.org/10.3389/fnbeh.2022.861155Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G (2009) Zebrafish: a complete animal model for in vivo drug discovery and development. Curr Drug Metab 10(2): 116–124. https://doi.org/10.2174/138920009787522197Kalueff AV, Stewart AM, Gerlai R (2014) Zebrafish as an emerging model for studying complex brain disorders. Trends Pharm Sci 35(2): 63–75. https://doi.org/10.1016/j.tips.2013.12.002Burgess HA, Burton EA (2023) A critical review of zebrafish neurological disease models–1. The premise: neuroanatomical, cellular, and genetic homology, and experimental tractability. Oxford Open Neurosci 2: kvac018. https://doi.org/10.1093/oons/kvac018Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S, Sealy I, Caccamo M, Churcher C, Scott C, Barrett JC, Koch R, Rauch GJ, White S, Chow W, Kilian B, Quintais LT, Guerra-Assunção JA, Zhou Y, Gu Y, Yen J, Vogel JH, Eyre T, Redmond S, Banerjee R, Chi J, Fu B, Langley E, Maguire SF, Laird GK, Lloyd D, Kenyon E, Donaldson S, Sehra H, Almeida-King J, Loveland J, Trevanion S, Jones M, Quail M, Willey D, Hunt A, Burton J, Sims S, McLay K, Plumb B, Davis J, Clee C, Oliver K, Clark R, Riddle C, Elliot D, Threadgold G, Harden G, Ware D, Begum S, Mortimore B, Kerry G, Heath P, Phillimore B, Tracey A, Corby N, Dunn M, Johnson C, Wood J, Clark S, Pelan S, Griffiths G, Smith M, Glithero R, Howden P, Barker N, Lloyd C, Stevens C, Harley J, Holt K, Panagiotidis G, Lovell J, Beasley H, Henderson C, Gordon D, Auger K, Wright D, Collins J, Raisen C, Dyer L, Leung K, Robertson L, Ambridge K, Leongamornlert D, McGuire S, Gilderthorp R, Griffiths C, Manthravadi D, Nichol S, Barker G, Whitehead S, Kay M, Brown J, Murnane C, Gray E, Humphries M, Sycamore N, Barker D, Saunders D, Wallis J, Babbage A, Hammond S, Mashreghi-Mohammadi M, Barr L, Martin S, Wray P, Ellington A, Matthews N, Ellwood M, Woodmansey R, Clark G, Cooper J, Tromans A, Grafham D, Skuce C, Pandian R, Andrews R, Harrison E, Kimberley A, Garnett J, Fosker N, Hall R, Garner P, Kelly D, Bird C, Palmer S, Gehring I, Berger A, Dooley CM, Ersan-Ürün Z, Eser C, Geiger H, Geisler M, Karotki L, Kirn A, Konantz J, Konantz M, Oberländer M, Rudolph-Geiger S, Teucke M, Lanz C, Raddatz G, Osoegawa K, Zhu B, Rapp A, Widaa S, Langford C, Yang F, Schuster SC, Carter NP, Harrow J, Ning Z, Herrero J, Searle SM, Enright A, Geisler R, Plasterk RH, Lee C, Westerfield M, de Jong PJ, Zon LI, Postlethwait JH, Nüsslein-Volhard C, Hubbard TJ, Roest Crollius H, Rogers J, Stemple DL (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496(7446): 498–503. https://doi.org/10.1038/nature12111Tomasiewicz HG, Flaherty DB, Soria JP, Wood JG (2002) Transgenic zebrafish model of neurodegeneration. J Neurosci Res 70(6): 734–745. https://doi.org/10.1002/jnr.10451Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, Fälting J, Distel M, Köster RW, Schmid B, Haass C (2009) A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Investig 119(5): 1382–1395. https://doi.org/10.1172/jci37537Köster RW, Fraser SE (2001) Tracing transgene expression in living zebrafish embryos. Dev Bio-l 233(2): 329–346. https://doi.org/10.1006/dbio.2001.0242Lopez A, Lee SE, Wojta K, Ramos EM, Klein E, Chen J, Boxer AL, Gorno-Tempini ML, Geschwind DH, Schlotawa L, Ogryzko NV, Bigio EH, Rogalski E, Weintraub S, Mesulam MM, Fleming A, Coppola G, Miller BL, Rubinsztein DC (2017) A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction. Brain 140(4): 1128–1146. https://doi.org/10.1093/brain/awx005Bai Q, Garver JA, Hukriede NA, Burton EA (2007) Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res 35 (9): 6501–6516. https://doi.org/10.1093/nar/gkm608Wu BK, Yuan RY, Lien HW, Hung CC, Hwang PP, Chen RP, Chang CC, Liao YF, Huang CJ (2016) Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo. J Biomed Sci 23: 25. https://doi.org/10.1186/s12929-016-0237-4Cosacak MI, Bhattarai P, Bocova L, Dzewas T, Mashkaryan V, Papadimitriou C, Brandt K, Hollak H, Antos CL, Kizil C (2017) Human TAU(P301L) overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain. Sci Rep 7(1): 12959. https://doi.org/10.1038/s41598-017-13311-5Ghetti B, Oblak AL, Boeve BF, Johnson KA, Dickerson BC, Goedert M (2015) Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol Appl Neurobiol 41(1): 24–46. https://doi.org/10.1111/nan.12213Nada SE, Williams FE, Shah ZA (2016) Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish. Drug Targets is CNS Neurol. Disord 15(1): 86–94. https://doi.org/10.2174/1871527314666150821105602Bhattarai P, Thomas AK, Cosacak MI, Papadimitriou C, Mashkaryan V, Zhang Y, Kizil C (2017) Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain. J Vis Exp 128: 56014. https://doi.org/10.3791/56014Bhattarai P, Thomas AK, Zhang Y, Kizil C (2017) The effects of aging on Amyloid-β42-induced neurodegeneration and regeneration in adult zebrafish brain. Neurogenesis 4(1): e1322666. https://doi.org/10.1080/23262133.2017.1322666Nery LR, Eltz NS, Hackman C, Fonseca R, Altenhofen S, Guerra HN, Freitas VM, Bonan CD, Vianna MR (2014) Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium. PloS One 9(9): e105862. https://doi.org/10.1371/journal.pone.0105862Stewart AM, Kalueff AV (2012) The developing utility of zebrafish models for cognitive enhancers research. Curr Neuropharmacol 10(3): 263–271. https://doi.org/10.2174/157015912803217323Галстян ДС, Колесникова ТО, Косицын ЮМ, Забегалов КН, Губайдуллина МА, Маслов ГО, Демин KA, Калуев АВ (2022) Оценка общей двигательной активности и тревожности зебраданио (Danio rerio) с использованием тестов незнакомого аквариума, открытого поля, черно-белого аквариума и построения косяка. Обзоры клин фармакол лекарств терапии 20: 123–133.[Galstyan DS, Kolesnikova TO, Kositsyn YM, Zabegalov KN, Gubaidullina MA, Maslov GO, Demin KA, Kalueff AV (2022) Assessment of general locomotor activity and anxiety in zebrafish (Danio rerio) in the light-dark box (tank), the shoaling test, in the novel tank and the open field tests. Rev Clin Pharmacol Drug Ther 20: 123–133. (In Russ)]. https://doi.org/10.17816/RCF202123-133Levin ED, Bencan Z, Cerutti DT (2007) Anxiolytic effects of nicotine in zebrafish. Physiol Behav 90(1): 54–58. https://doi.org/10.1016/j.physbeh.2006.08.026Галстян ДС, Колесникова ТО, Косицын ЮМ, Забегалов КН, Губайдуллина МА, Маслов ГО, Калуев АВ (2022) Когнитивные тесты зебраданио (Danio rerio): Т- и Y-образные лабиринты. Обзоры клин фармакол лекарств терапии 20: 163–168. [Galstyan DS, Kolesnikova TO, Kositsyn YM, Zabegalov KN, Gubaidullina MA, Maslov GO, Kalueff AV (2022) Cognitive tests in zebrafish (Danio rerio): T- and Y-mazes. Rev Clin Pharmacol Drug Ther 20: 163–168. (In Russ)]. https://doi.org/10.17816/RCF202163-168Grossman L, Stewart A, Gaikwad S, Utterback E, Wu N, Dileo J, Frank K, Hart P, Howard H, Kalueff AV (2011) Effects of piracetam on behavior and memory in adult zebrafish. Brain Res Bull 85(1-2) :58–63. https://doi.org/10.1016/j.brainresbull.2011.02.008Lalonde R (2002) The neurobiological basis of spontaneous alternation. Neurosci Biobehav Rev 26(1): 91–104. https://doi.org/10.1016/s0149-7634(01)00041-0Lee Y, Lee S, Park JW, Hwang JS, Kim SM, Lyoo IK, Lee CJ, Han IO (2018) Hypoxia-Induced Neuroinflammation and Learning-Memory Impairments in Adult Zebrafish Are Suppressed by Glucosamine. Mol Neurobiol 55(11): 8738–8753. https://doi.org/10.1007/s12035-018-1017-9Lee Y, Kim D, Kim YH, Lee H, Lee CJ (2010) Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish. Eur J Pharmacol 643(2-3): 225–231. https://doi.org/10.1016/j.ejphar.2010.06.041Kim YH, Lee Y, Kim D, Jung MW, Lee CJ (2010) Scopolamine-induced learning impairment reversed by physostigmine in zebrafish. Neurosci Res 67:2:156–161. https://doi.org/10.1016/j.neures.2010.03.003Rajesh V, Mridhulmohan M, Jayaseelan S, Sivakumar P, Ganesan V (2018) Mefenamic Acid Attenuates Chronic Alcohol Induced Cognitive Impairment in Zebrafish: Possible Role of Cholinergic Pathway. Neurochem Res 43(7): 1392–1404. https://doi.org/10.1007/s11064-018-2554-3de Castro MR, Lima JV, Salomão de Freitas DP, de Souza Valente R, Dummer NS, de Aguiar RB, dos Santos LC, Marins LF, Geracitano LA, Monserrat JM, Barros DM (2009) Behavioral and neurotoxic effects of arsenic exposure in zebrafish (Danio rerio, Teleostei: Cyprinidae). Comp Biochem Physiol PtC Toxicol Pharmacol 150(3): 337–342. https://doi.org/10.1016/j.cbpc.2009.05.017Zelenchuk TA, Brusés JL (2011) In vivo labeling of zebrafish motor neurons using an mnx1 enhancer and Gal4/UAS. Genesis 49(7): 546–554. https://doi.org/10.1002/dvg.20766Imamura S, Yabu T, Yamashita M (2012) Protective role of cell division cycle 48 (CDC48) protein against neurodegeneration via ubiquitin-proteasome system dysfunction during zebrafish development. J Biol Chem 287(27): 23047–23056. https://doi.org/10.1074/jbc.M111.332882Mathai BJ, Meijer AH, Simonsen A (2017) Studying Autophagy in Zebrafish. Cells 6(3): 21. https://doi.org/10.3390/cells6030021Jester HM, Gosrani SP, Ding H, Zhou X, Ko MC, Ma T (2022) Characterization of Early Alzheimer’s Disease-Like Pathological Alterations in Non-Human Primates with Aging: A Pilot Study. J Alz Dis 88(3): 957–970.https://doi.org/10.3233/jad-215303Plucińska G, Paquet D, Hruscha A, Godinho L, Haass C, Schmid B, Misgeld T (2012) In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system. J Neurosci 32(46): 16203–16212. https://doi.org/10.1523/jneurosci.1327-12.2012Barbereau C, Yehya A, Silhol M, Cubedo N, Verdier JM, Maurice T, Rossel M (2020) Neuroprotective brain-derived neurotrophic factor signaling in the TAU-P301L tauopathy zebrafish model. Pharmacol Res 158: 104865. https://doi.org/10.1016/j.phrs.2020.104865Giustiniani J, Chambraud B, Sardin E, Dounane O, Guillemeau K, Nakatani H, Paquet D, Kamah A, Landrieu I, Lippens G, Baulieu EE, Tawk M (2014) Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy. Proc Natl Acad Sci U S A 111(12) : 4584–4589.https://doi.org/10.1073/pnas.1402645111Hassan-Abdi R, Brenet A, Bennis M, Yanicostas C, Soussi-Yanicostas N (2019) Neurons Expressing Pathological Tau Protein Trigger Dramatic Changes in Microglial Morphology and Dynamics. Front Neurosci 13: 1199. https://doi.org/10.3389/fnins.2019.01199Smith DG, Buffet M, Fenwick AE, Haigh D, Ife RJ, Saunders M, Slingsby BP, Stacey R, Ward RW (2001) 3-Anilino-4-arylmaleimides: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorgan Med Chem Lett 11(5): 635–639. https://doi.org/10.1016/s0960-894x(00)00721-6Alavi Naini SM, Yanicostas C, Hassan-Abdi R, Blondeel S, Bennis M, Weiss RJ, Tor Y, Esko JD, Soussi-Yanicostas N (2018) Surfen and oxalyl surfen decrease tau hyperphosphorylation and mitigate neuron deficits in vivo in a zebrafish model of tauopathy. Transl Neurodegenerat 7: 6. https://doi.org/10.1186/s40035-018-0111-2Wu BK, Yuan RY, Chang YP, Lien HW, Chen TS, Chien HC, Tong TS, Tsai HP, Fang CL, Liao YF, Chang CC, Chen RP, Huang CJ (2016) Epicatechin isolated from Tripterygium wilfordii extract reduces tau-GFP-induced neurotoxicity in zebrafish embryo through the activation of Nrf2. Biochem Biophys Res Commun 477(2): 283–289. https://doi.org/10.1016/j.bbrc.2016.06.058Sáiz-Vázquez O, Gracia-García P, Ubillos-Landa S, Puente-Martínez A, Casado-Yusta S, Olaya B, Santabárbara J (2021) Depression as a Risk Factor for Alzheimer’s Disease: A Systematic Review of Longitudinal Meta-Analyses. J Clin Med. 10: 9. https://doi.org/10.3390/jcm10091809Brendel M, Sauerbeck J, Greven S, Kotz S, Scheiwein F, Blautzik J, Delker A, Pogarell O, Ishii K, Bartenstein P, Rominger A (2018) Serotonin Selective Reuptake Inhibitor Treatment Improves Cognition and Grey Matter Atrophy but not Amyloid Burden During Two-Year Follow-Up in Mild Cognitive Impairment and Alzheimer’s Disease Patients with Depressive Symptoms. J Alz Dis 65(3): 793–806. https://doi.org/10.3233/jad-170387Матвеева МВ, Самойлова ЮГ, Жукова НГ, Олейник ОА, Ротканк МА (2017) Таупатия и когнитивные нарушения при экспериментальном сахарном диабете. Сахарн диабет 20(3): 181–184. [Matveeva MV, SamoiIova YG, Zhukova NG, Oleynik OA, Rotkank MA (2017) Tauopathy and cognitive impairment in experimental diabetes mellitus. Diabetes mellitus 20(3): 181–184. (In Russ)].Denver P, English A, McClean PL (2018) Inflammation, insulin signaling and cognitive function in aged APP/PS1 mice. Brain Behav Immun 70: 423–434. https://doi.org/10.1016/j.bbi.2018.03.032Di Domenico F, Tramutola A, Foppoli C, Head E, Perluigi M, Butterfield DA (2018) mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia. Free Radic Biol Med 114 :94–101. https://doi.org/10.1016/j.freeradbiomed.2017.08.009Morawe MP, Liao F, Amberg W, van Bergeijk J, Chang R, Gulino M, Hamilton C, Hoft C, Lumpkin C, Mastis B, McGlame E, Nuber J, Plaas C, Ravikumar B, Roy K, Schanzenbächer M, Tierno J, Lakics V, Dellovade T, Townsend M (2022) Pharmacological mTOR-inhibition facilitates clearance of AD-related tau aggregates in the mouse brain. Eur J Pharmacol 934: 175301. https://doi.org/10.1016/j.ejphar.2022.175301Megur A, Baltriukienė D, Bukelskienė V, Burokas A (2020) The Microbiota-Gut-Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame? Nutrients 13(1): 37. https://doi.org/10.3390/nu13010037Seo DO, O’Donnell D, Jain N, Ulrich JD, Herz J, Li Y, Lemieux M, Cheng J, Hu H, Serrano JR, Bao X, Franke E, Karlsson M, Meier M, Deng S, Desai C, Dodiya H, Lelwala-Guruge J, Handley SA, Kipnis J, Sisodia SS, Gordon JI, Holtzman DM (2023) ApoE isoform- and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy. Science 379: 6628: eadd1236. https://doi.org/10.1126/science.add1236Cornuault JK, Byatt G, Paquet ME, De Koninck P, Moineau S (2022) Zebrafish: a big fish in the study of the gut microbiota. Curr Opin Biotechnol 73: 308–313. https://doi.org/10.1016/j.copbio.2021.09.007Griciuc A, Tanzi RE (2021) The role of innate immune genes in Alzheimer’s disease. Curr Opin Neurol 34(2): 228–236. https://doi.org/10.1097/wco.0000000000000911Schmidt R, Strähle U, Scholpp S (2013) Neurogenesis in zebrafish - from embryo to adult. Neural Dev 8: 3. https://doi.org/10.1186/1749-8104-8-3Schindler SE, Karikari TK (2022) Comorbidities confound Alzheimer’s blood tests. Nat Med 28(7): 1349–1351. https://doi.org/10.1038/s41591-022-01875-3Mahali S, Martinez R, King M, Verbeck A, Harari O, Benitez BA, Horie K, Sato C, Temple S, Karch CM (2022) Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration. Transl Psychiatry 12(1): 508. https://doi.org/10.1038/s41398-022-02274-5Johnson NR, Yuan P, Castillo E, Lopez TP, Yue W, Bond A, Rivera BM, Sullivan MC, Hirouchi M, Giles K, Aoyagi A, Condello C (2023) CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model. Nat Commun 14(1): 118. https://doi.org/10.1038/s41467-022-35753-wTai C, Chang CW, Yu GQ, Lopez I, Yu X, Wang X, Guo W, Mucke L (2020) Tau Reduction Prevents Key Features of Autism in Mouse Models. Neuron 106(3): 421–437. https://doi.org/10.1016/j.neuron.2020.01.038