Аннотация
Введение. Многие химические соединения воздействуют на нейроны головного мозга иначе, чем на остальные клеточные популяции. Это обеспечено защитным потенциалом гематоэнцефалического барьера (ГЭБ). Теоретически рассмотрено одно из соединений, способное проходить через ГЭБ, бактериальный липополисахарид (ЛПС), который может вызывать необратимые морфологические изменения в нейронах коры больших полушарий головного мозга. Цель исследования: изучить механизмы нейронального повреждения при воздействии несептических доз ЛПС. Материал и методы. Произведен анализ более 50 литературных источников по базам данных PubMed и Elibrary за последние 15 лет. Результаты. Астроциты распознают ЛПС благодаря Toll-подобным рецепторам, а макрофаги глии, кроме того, способны захватывать участки внешней бактериальной мембраны с ЛПС. Однако вариации дозы ЛПС, способа и частоты его введения по-разному влияют на морфологию коры больших полушарий головного мозга. В частности, актуально изучение изменений, аналогичных таковым при старении и нейродегенеративных процессах. Заключение. Рассмотрены структурные изменения нейронов и глии при применении ЛПС у взрослых животных. Авторы пришли к выводу, что многократное системное введение несептических доз ЛПС в наибольшей степени подходят для моделирования аналогичных старению изменений, но необходима разработка стандартизованной модели такого введения.
Авторы и аффилиации
А.А. Венедиктов(1), Е.А. Кузьмин(1), К.С. Покидова(1), Д.М. Оганесян(1),
А.Т. Степаньян(1), Т.В. Боронихина(2), Г.А. Пьявченко(1),С.Л. Кузнецов(1),
1-ФГАОУ ВО «Первый Московский государственный медицинский университет
им. И.М. Сеченова» Минздрава России (Сеченовский университет),
Российская Федерация, 119048, Москва, ул. Трубецкая, д. 8, стр. 2;
2-Негосударственное образовательное частное учреждение высшего образования
«Московский финансово-промышленный университет «Синергия»,
Российская Федерация, 129090, Москва, ул. Мещанская, д. 9/14, стр. 1
Литература
Behfar Q., Ramirez Zuniga A., Martino-Adami P.V. Aging, Senescence, and Dementia. The J. of prevention of Alzheimer’s disease. 2022; 9 (3): 523–31. https://doi.org/10.14283/jpad.2022.42
Gomez C.R. Role of heat shock proteins in aging and chronic inflammatory diseases. GeroScience. 2021; 43 (5): 2515–32. https://doi.org/10.1007/s11357-021-00394-2
Venediktov A.A., Bushueva O.Y., Kudryavtseva V.A., Kuzmin E.A., Moiseeva A.V., Baldycheva A., Meglinski I., Piavchenko G.A. Closest horizons of Hsp70 engagement to manage neurodegeneration. Frontiers in molecular neuroscience. 2023; 16: 1230436. https://doi.org/10.3389/fnmol.2023.1230436
Kosyreva A.M, Sentyabreva A.V., Tsvetkov I.S., Makarova O.V. Alzheimer’s disease and inflammaging. Brain sciences. 2022; 12 (9): 1237. https://doi.org/10.3390/brainsci12091237
Kamm G.B., Siemens J. Neuroscience: Detection of systemic inflammation by the brain. Current biology. 2022; 32 (13): 751–3. https://doi.org/10.1016/j.cub.2022.05.028
Xin Y.Y., Wang J.X., Xu A.J. Electroacupuncture ameliorates neuroinflammation in animal models. Acupuncture in medicine: J. of the British Medical Acupuncture Society. 2022; 40 (5): 474–83. https://doi.org/10.1177/09645284221076515
Lassmann H. Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis. J. of neurology. 1983; 229 (4): 207–20. https://doi.org/10.1007/BF00313549
Praet J., Guglielmetti C., Berneman Z., Van der Linden A., Ponsaerts P. Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis. Neuroscience and biobehavioral reviews. 2014; 47: 485–505. https://doi.org/10.1016/j.neubiorev.2014.10.004
Seemann S., Zohles F., Lupp, A. Comprehensive comparison of three different animal models for systemic inflammation. Journal of biomedical science. 2017; 24 (1): 60. https://doi.org/10.1186/s12929-017-0370-8
Da Silva A.A.F., Fiadeiro M.B., Bernardino L.I., Baltazar G.M.F., Cristóvão A.C.B. Lipopolysaccharide-induced animal models for neuroinflammation – An overview. Journal of neuroimmunology. 2024; 387: 578273. https://doi.org/10.1016/j.jneuroim.2023.578273
Skrzypczak-Wiercioch A., Sałat K. Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use. Molecules (Basel, Switzerland). 2022; 27 (17): 5481. https://doi.org/10.3390/molecules27175481
Klein G., Lindner B., Brade H., Raina S. Molecular basis of lipopolysaccharide heterogeneity in Escherichia coli: envelope stress-responsive regulators control the incorporation of glycoforms with a third 3-deoxy-α-D-manno-oct-2-ulosonic acid and rhamnose. The J. of biological chemistry. 2011; 286 (50): 42787–807. https://doi.org/10.1074/jbc.M111.291799
Gorman A., Golovanov A.P. Lipopolysaccharide Structure and the Phenomenon of Low Endotoxin Recovery. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik. 2022; 180: 289–307. https://doi.org/10.1016/j.ejpb.2022.10.006
Avila-Calderón E.D., Ruiz-Palma M.D.S., Aguilera-Arreola M.G., Velázquez-Guadarrama N., Ruiz E.A., Gomez-Lunar Z., Witonsky S., Contreras-Rodriguez A. Outer Membrane Vesicles of Gram-Negative Bacteria: An Outlook on Biogenesis. Frontiers in microbiology. 2021; 12: 557902. https://doi.org/10.3389/fmicb.2021.557902
Schrоder N.W., Schumann R.R. Non-LPS targets and actions of LPS binding protein (LBP). Journal of endotoxin research. 2005; 11 (4): 237–42. https://doi.org/10.1179/096805105X37420
Ryu J.K., Kim S.J., Rah S.H., Kang J.I., Jung H.E., Lee D., Lee H.K., Lee J.O., Park B.S., Yoon T.Y., Kim H.M. Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer. Immunity. 2017; 46 (1): 38–50. https://doi.org/10.1016/j.immuni.2016.11.007
Jagtap P., Prasad P., Pateria A., Deshmukh S.D., Gupta S. A Single Step in vitro Bioassay Mimicking TLR4-LPS Pathway and the Role of MD2 and CD14 Coreceptors. Frontiers in immunology. 2020; 11: 5. https://doi.org/10.3389/fimmu.2020.00005
Mazgaeen L., Gurung P. Recent Advances in Lipopolysaccharide Recognition Systems. International J. of molecular sciences. 2020; 21 (2): 379. https://doi.org/10.3390/ijms21020379
Adhikarla S.V., Jha N.K., Goswami V.K., Sharma A., Bhardwaj A., Dey A., Villa C., Kumar Y., Jha S.K. TLR-Mediated Signal Transduction and Neurodegenerative Disorders. Brain sciences. 2021; 11 (11): 1373. https://doi.org/10.3390/brainsci11111373
Al-Khafaji A.B., Tohme S., Yazdani H.O., Miller D., Huang H., Tsung A. Superoxide induces Neutrophil Extracellular Trap Formation in a TLR-4 and NOX-dependent mechanism. Molecular medicine (Cambridge, Massachusetts). 2016; 22: 621–31. https://doi.org/10.2119/molmed.2016.00054
Yoo J.Y., Cha D.R., Kim B., An E.J., Lee S.R., Cha J.J., Kang Y.S., Ghee J. Y., Han J.Y., Bae Y.S. LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1. Cell reports. 2020; 33 (3): 108245. https://doi.org/10.1016/j.celrep.2020.108245
Wang B., Zeng H., Zuo X., Yang X., Wang X., He D., Yuan J. TLR4-Dependent DUOX2 Activation Triggered Oxidative Stress and Promoted HMGB1 Release in Dry Eye. Frontiers in medicine. 2022; 8: 781616. https://doi.org/10.3389/fmed.2021.781616
Pfalzgraff A., Correa W., Heinbockel L., Schromm A.B., Lübow C., Gisch N., Martinez-de-Tejada G., Brandenburg K., Weindl G. LPS-neutralizing peptides reduce outer membrane vesicle-induced inflammatory responses. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2019; 1864 (10): 1503–13. https://doi.org/10.1016/j.bbalip.2019.05.018
. Yang R., Zhang X. A potential new pathway for heparin treatment of sepsis-induced lung injury: inhibition of pulmonary endothelial cell pyroptosis by blocking hMGB1-LPS-induced caspase-11 activation. Frontiers in cellular and infection microbiology. 2022; 12: 984835. https://doi.org/10.3389/fcimb.2022.984835
. Zamyatina A., Heine H. Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways. Frontiers in immunology. 2020; 11: 585146. https://doi.org/10.3389/fimmu.2020.585146
Gabarin R.S., Li M., Zimmel P.A., Marshall J.C., Li Y., Zhang H. Intracellular and Extracellular Lipopolysaccharide Signaling in Sepsis: Avenues for Novel Therapeutic Strategies. J. of innate immunity. 2021; 13 (6): 323–32. https://doi.org/10.1159/000515740
Wong M.L., Rettori V., al-Shekhlee A., Bongiorno P.B., Canteros G., McCann S.M., Gold P.W., Licinio J. Inducible nitric oxide synthase gene expression in the brain during systemic inflammation. Nature medicine. 1996; 2 (5): 581–4. https://doi.org/10.1038/nm0596-581
Mou Y., Du Y., Zhou L., Yue J., Hu X., Liu Y., Chen S., Lin X., Zhang G., Xiao H., Dong B. Gut Microbiota Interact with the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging. Frontiers in immunology. 2022; 13: 796288. https://doi.org/10.3389/fimmu.2022.796288
Ineichen B.V., Okar S.V., Proulx S.T., Engelhardt B., Lassmann H., Reich D.S. Perivascular spaces and their role in neuroinflammation. Neuron. 2022; 110 (21): 3566–81. https://doi.org/10.1016/j.neuron.2022.10.024
Hashioka S., Wu Z., Klegeris A. Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease. Current neuropharmacology. 2021; 19 (7): 908–24. https://doi.org/10.2174/1570159X18666201111104509
Gasparotto J., Ribeiro C.T., da Rosa-Silva H.T., Bortolin R.C., Rabelo T.K., Peixoto D.O., Moreira J.C.F., Gelain D.P. Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas. Molecular neurobiology. 2019; 56 (5): 3079–89. https://doi.org/10.1007/s12035-018-1291-6
Diaz-Castro B., Bernstein A.M., Coppola G., Sofroniew M.V., Khakh B.S. Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation. Cell reports. 2021; 36 (6): 109508. https://doi.org/10.1016/j.celrep.2021.109508
Feldman R.A. Microglia orchestrate neuroinflammation. eLife. 2022; 11: e81890. https://doi.org/10.7554/eLife.81890
Peng X., Luo Z., He S., Zhang L., Li Y. Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy. Frontiers in cellular and infection microbiology. 2021; 11: 768108. https://doi.org/10.3389/fcimb.2021.768108
Zhan X., Stamova B., Sharp F.R. Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer’s Disease Brain: A Review. Frontiers in aging neuroscience. 2018; 10: 42. https://doi.org/10.3389/fnagi.2018.00042
Galea I. The blood-brain barrier in systemic infection and inflammation. Cellular & molecular immunology. 2021; 18 (11): 2489–501. https://doi.org/10.1038/s41423-021-00757-x
Gajewski M.P., Barger S.W. Design, synthesis, and characterization of novel system xC- transport inhibitors: inhibition of microglial glutamate release and neurotoxicity. Journal of neuroinflammation. 2023; 20 (1): 292. https://doi.org/10.1186/s12974-023-02972-x
Yi Y.S. Caspase-11 non-canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage-mediated inflammatory responses. Immunology. 2017; 152 (2): 207–17. https://doi.org/10.1111/imm.12787
Manouchehrian O., Ramos M., Bachiller S., Lundgaard I., Deierborg T. Acute systemic LPS-exposure impairs perivascular CSF distribution in mice. Journal of neuroinflammation. 2021; 18 (1): 34. https://doi.org/10.1186/s12974-021-02082-6
Haileselassie B., Joshi A.U., Minhas P.S., Mukherjee R., Andreasson K.I., Mochly-Rosen D. Mitochondrial dysfunction mediated through dynamin-related protein 1 (Drp1) propagates impairment in blood brain barrier in septic encephalopathy. Journal of neuroinflammation. 2020; 17 (1): 36. https://doi.org/10.1186/s12974-019-1689-8
Banks W.A., Robinson S.M. Minimal penetration of lipopolysaccharide across the murine blood-brain barrier. Brain, behavior, and immunity. 2010; 24 (1): 102–9. https://doi.org/10.1016/j.bbi.2009.09.001
Zhao J., Bi W., Xiao S., Lan X., Cheng X., Zhang J., Lu D., Wei W., Wang, Y., Li H., Fu Y., Zhu L. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Scientific reports. 2019; 9 (1): 5790. https://doi.org/10.1038/s41598-019-42286-8
Дятлова А.С., Новикова Н.С., Юшков Б.Г., Корнева Е.А., Черешнев В.А. Гематоэнцефалический барьер в нейроиммунных взаимодействиях и патологических процессах. Вестник Российской академии наук. 2022. 92 (5): 590–9. https://doi.org/10.1134/S1019331622050100 [Dyatlova A.S., Novikova N.S., Yushkov B.G., Korneva E.A., Chereshnev V.A. The Blood-Brain Barrier in Neuroimmune Interactions and Pathological Processes. Herald of the Russian Academy of Sciences. 2022; 92 (5): 590–9. https://doi.org/10.1134/S1019331622050100]
Adán Areán J.S., Vico T.A., Marchini T., Calabró V., Evelson P.A., Vanasco V., Alvarez S. Energy management and mitochondrial dynamics in cerebral cortex during endotoxemia. Archives of biochemistry and biophysics. 2021; 705: 108900. https://doi.org/10.1016/j.abb.2021.108900
Munro D., Baldy C., Pamenter M.E., Treberg J.R. The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses. Aging cell. 2019; 18 (3): e12916. https://doi.org/10.1111/acel.12916
Dietrich J.B. The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier. J. of neuroimmunology. 2002; 128 (1–2): 58–68. https://doi.org/10.1016/s0165-5728(02)00114-5
Haruwaka K., Ikegami A., Tachibana Y., Ohno N., Konishi H., Hashimoto A., Matsumoto M., Kato, D., Ono R., Kiyama H., Moorhouse A.J., Nabekura J., Wake H. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nature communications. 2019; 10 (1): 5816. https://doi.org/10.1038/s41467-019-13812-z
Пьявченко Г.А., Алексеев А.Г., Серегина Е.С., Стельмащук О.А., Жеребцов Е.А. Оценка токсического действия сукцината цинка на кору больших полушарий головного мозга крыс. Сеченовский вестник. 2019; 10 (2): 29–35. https://doi.org/10.26442/22187332.2019.2.29-35 [Piavchenko G.A., Alekseev A.G., Seryogina E.S., Stelmashchuk O.A., Zherebtsov Ye.A. Evaluation of the zinc succinate toxic effect on the cerebral cortex of rat. Sechenov Medical J. 2019; 10 (2): 29–35. https://doi.org/10.26442/22187332.2019.2.29-35]
Clarke L.E., Liddelow S.A., Chakraborty C., Münch A.E., Heiman M., Barres B.A. Normal aging induces A1-like astrocyte reactivity. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115 (8): 1896–905. https://doi.org/10.1073/pnas.1800165115
Qin L., Wu X., Block M.L., Liu Y., Breese G.R., Hong J.S., Knapp D.J., Crews F.T. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007; 55 (5): 453–62. https://doi.org/10.1002/glia.20467
Jeong H.K., Jou I., Joe E.H. Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra. Experimental & molecular medicine. 2010; 42 (12): 823–32. https://doi.org/10.3858/emm.2010.42.12.085
Jung H., Lee D., You H., Lee M., Kim H., Cheong E., Um, J.W. LPS induces microglial activation and GABAergic synaptic deficits in the hippocampus accompanied by prolonged cognitive impairment. Scientific reports. 2023; 13 (1): 6547. https://doi.org/10.1038/s41598-023-32798-9
Huang H.J., Chen Y.H., Liang K.C., Jheng Y.S., Jhao J.J., Su M.T., Lee-Chen G.J., Hsieh-Li H.M. Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection. PloS one. 2012; 7 (7): e39656. https://doi.org/10.1371/journal.pone.0039656
Ryu K.Y., Lee H.J., Woo H., Kang R.J., Han K.M., Park H., Lee S.M., Lee J.Y., Jeong Y.J., Nam H.W., Nam Y., Hoe H.S. Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling. J. of neuroinflammation. 2019; 16 (1): 190. https://doi.org/10.1186/s12974-019-1561-x
Nam H.Y., Nam J.H., Yoon G., Lee J.Y., Nam Y., Kang H.J., Cho H.J., Kim J., Hoe H.S. Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. Journal of neuroinflammation. 2018; 15 (1): 271. https://doi.org/10.1186/s12974-018-1308-0
DiSabato D.J., Quan N., Godbout J.P. Neuroinflammation: the devil is in the details. Journal of neurochemistry. 2016; 139 (2): 136–53. https://doi.org/10.1111/jnc.13607
Пьявченко Г.А., Венедиктов А.А., Кузьмин Е.А., Кузнецов С.Л. Морфофункциональные изменения у мышей после однократного введения высоких и низких доз Hsp70. Сеченовский вестник. 2023; 14 (4): 31–41. https://doi.org/10.47093/2218-7332.2023.918.13 [Piavchenko G.A., Venediktov A.A., Kuzmin E.A., Kuznetsov S.L. Morphofunctional features in mice treated by low and high Hsp70 doses. Sechenov Medical J. 2023; 14 (4): 31–41. https://doi.org/10.47093/2218-7332.2023.918.13]
Стефанова Н.А., Корболина Е.Е., Ершов Н.И., Рогаев Е.И., Колосова Н.Г. Изменения транскриптома префронтальной коры мозга при развитии признаков болезни Альцгеймера у крыс OXYS. Вавиловский журнал генетики и селекции. 2015; 19 (4): 445–54. https://doi.org/10.118699/VJ15.059 [Stefanova N.A., Korbolina E.E., Ershov N.I., Rogaev Ye.I., Kolosova N.G. Changes in the transcriptome of the prefrontal cortex of OXYS rats as the signs of Alzheimer’s disease development. Vavilovskii Zhurnal Genetiki i Selektsii. Vavilov J. of genetics and Breeding. 2015; 19 (4): 445–54. https://doi.org/10.118699/VJ15.059].