Ultrastructural features of astroglial endosomal system state in sepsis-associated encephalopathy

Authors

DOI:

https://doi.org/10.14739/2310-1237.2020.1.203742

Keywords:

astroglia, sepsis associated encephalopathy, multivesicular bodies

Abstract

 

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, with a range of dysfunctional brain disorders. Astrocytes, as the main homeostatic brain cells, play a key role during adaptation of brain tissue to acute damage.

The aim. To determine the ultrastructural state of endosomal system of astrocytes in the rat brain under experimental conditions of systemic inflammation.

Materials and methods. Male Wistar rats were divided into 2 groups: control group (5 sham-operated animals); the main group with cecal ligation and puncture (CLP, 10 animals). The study of cortex and subcortical white matter of sensorimotor zone in the period between 12 and 24 h after operation was carried out using TEM.

Results. In CLP group, starting from 12 h after operation the number of multivesicular bodies (MVBs) increased in astroglial pericaryons and processes. Thus, deceased animals showed a tendency to increase in number of endosomes compared with control and the predominance of their localization in the pericarions of astrocytes. Astroglia of survived animals of CLP group showed the lesser degree of intracellular edema and accumulation of MVBs into perivascular astroglial endfeet, where they exceeded control up to 3 times.

Conclusion. In conditions of SAE, starting from 12 h after operation, brain astrocytes show obvious reactive changes with an activation of their endosomal-exosomal machinery, which reflects a high degree of adaptive activity of astroglia and compensatory phase of the pathological state of tissue. One of the ultrastructural signs of this phenomenon is the increased density of MVBs and redistribution of latter predominantly in capillary astrocytic endfeet. The accumulation of MVBs in astrocytic processes may indicate the activation of their intercellular and gliovascular interactions through endo- and exocytosis in the acute phase of adaptive processes under conditions of SAE. This fact emphasizes the special role of astroglia in the compensation of impaired brain homeostasis in SAE.

References

  1. Lamar, C. D., Hurley, R. A., & Taber, K. H. (2011). Sepsis-Associated Encephalopathy: Review of the Neuropsychiatric Manifestations and Cognitive Outcome. Journal of Neuropsychiatry and Clinical Neurosciences, 23(3), 236-241. https://doi.org/10.1176/appi.neuropsych.23.3.237
  2. Shuliatnikova, T. V, & Shavrin, V. O. (2018). Sepsis associated encephalopathy and abdominal sepsis: current state of problem. Art of Medicine, (3), 158-165.
  3. Sartelli, M., Abu-Zidan, F. M., Catena, F., Griffiths, E. A., Di Saverio, S., Coimbra, R., & Ansaloni, L. (2015). Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections: a prospective multicentre study (WISS Study). World Journal of Emergency Surgery, 10, Article 61. https://doi.org/10.1186/s13017-015-0055-0
  4. Shulyatnikova, T., & Verkhratsky, A. (2020). Astroglia in Sepsis Associated Encephalopathy. Neurochemical Research, 45(1), 83-99. https://doi.org/10.1007/s11064-019-02743-2
  5. Sonneville, R., Verdonk, F., Rauturier, C., Klein, I. F., Wolff, M., Annane, D., Chretien, F., & Sharshar, T. (2013). Understanding brain dysfunction in sepsis. Annals of Intensive Care, 3, Article 15. https://doi.org/10.1186/2110-5820-3-15
  6. Chaudhry, N., & Duggal, A. K. (2014). Sepsis Associated Encephalopathy. Advances in Medicine, 2014, 1-16. https://doi.org/10.1155/2014/762320
  7. Verkhratsky, A., & Nedergaard, M. (2018). Physiology of Astroglia. Physiological Reviews, 98(1), 239-389. https://doi.org/10.1152/physrev.00042.2016
  8. Sofroniew, M. V. (2015). Astrocyte barriers to neurotoxic inflammation. Nature Reviews Neuroscience, 16(5), 249-263. https://doi.org/10.1038/nrn3898
  9. Zorec, R., Zupanc, T. A., & Verkhratsky, A. (2019). Astrogliopathology in the infectious insults of the brain. Neuroscience Letters, 689, 56-62. https://doi.org/10.1016/j.neulet.2018.08.003
  10. Vardjan, N., & Zorec, R. (2015). Excitable astrocytes: Ca2+- and cAMP-regulated exocytosis. Neurochemical Research, 40(12), 2414-2424. https://doi.org/10.1007/s11064-015-1545-x
  11. Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J. P., & Zorec, R. (2016). Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. Embo Journal, 35(3), 239-257. https://doi.org/10.15252/embj.201592705
  12. Vardjan, N., Parpura, V., Verkhratsky, A., & Zorec, R. (2019). Gliocrine system: Astroglia as secretory cells of the CNS. In Advances in Experimental Medicine and Biology (Vol. 1175, pp. 93-115). Springer New York LLC. https://doi.org/10.1007/978-981-13-9913-8_4
  13. Turchinovich, A., Drapkina, O., & Tonevitsky, A. (2019). Transcriptome of Extracellular Vesicles: State-of-the-Art. Frontiers in Immunology, 10, Article 202. https://doi.org/10.3389/fimmu.2019.00202
  14. Liu, T., Zhang, Q., Zhang, J. K., Li, C., Miao, Y. R., Lei, Q., Li, Q. B., & Guo, A. Y. (2019). EVmiRNA: a database of miRNA profiling in extracellular vesicles. Nucleic Acids Research, 47(D1), D89-D93. https://doi.org/10.1093/nar/gky985
  15. Lian, H., Yang, L., Cole, A., Sun, L., Chiang, A. C. A., Fowler, S. W., Shim, D. J., Rodriguez-Rivera, J., Taglialatela, G., Jankowsky, J. L., Lu, H. C., & Zheng, H. (2015). NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer’s Disease. Neuron, 85(1), 101–115. https://doi.org/10.1016/j.neuron.2014.11.018
  16. Vardjan, N., Gabrijel, M., Potokar, M., Svajger, U., Kreft, M., Jeras, M., de Pablo, Y., Faiz, M., Pekny, M., & Zorec, R. (2012). IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments. Journal of Neuroinflammation, 9. https://doi.org/10.1186/1742-2094-9-144
  17. Božić, M., Verkhratsky, A., Zorec, R., & Stenovec, M. (2019). Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-019-03350-8
  18. Huotari, J., & Helenius, A. (2011). Endosome maturation. EMBO Journal, 30(17), 3481-3500. https://doi.org/10.1038/emboj.2011.286
  19. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Brugger, B., & Simons, M. (2008). Ceramide triggers budding of exosome vesicles into multivesicular Endosomes. Science, 319(5867), 1244-1247. https://doi.org/10.1126/science.1153124
  20. Luzio, J. P., Gray, S. R., & Bright, N. A. (2010). Endosome-lysosome fusion. Biochemical Society Transactions, 38, 1413-1416. https://doi.org/10.1042/bst0381413
  21. Hanson, P. I., & Cashikar, A. (2012). Multivesicular Body Morphogenesis. Annual Review of Cell and Developmental Biology, Vol 28, 28, 337-362. https://doi.org/10.1146/annurev-cellbio-092910-154152
  22. Doyle, L. M., & Wang, M. Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8(7), Article 727. https://doi.org/10.3390/cells8070727
  23. EP and Council. (2010). Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. OJ L276:33.
  24. Rittirsch, D., Huber-Lang, M. S., Flierl, M. A., & Ward, P. A. (2009). Immunodesign of experimental sepsis by cecal ligation and puncture. Nature Protocols, 4(1), 31-36. https://doi.org/10.1038/nprot.2008.214
  25. Toscano, M. G., Ganea, D., & Gamero, A. M. (2011). Cecal Ligation Puncture Procedure. Jove-Journal of Visualized Experiments, (51), Article e2860. https://doi.org/10.3791/2860
  26. Su, W., Aloi, M. S., & Garden, G. A. (2016). MicroRNAs mediating CNS inflammation: Small regulators with powerful potential. Brain Behavior and Immunity, 52, 1-8. https://doi.org/10.1016/j.bbi.2015.07.003
  27. Gaudet, A. D., Fonken, L. K., Watkins, L. R., Nelson, R. J., & Popovich, P. G. (2018). MicroRNAs: Roles in Regulating Neuroinflammation. Neuroscientist, 24(3), 221-245. https://doi.org/10.1177/1073858417721150
  28. Nuzziello, N., & Liguori, M. (2019). The MicroRNA Centrism in the Orchestration of Neuroinflammation in Neurodegenerative Diseases. Cells, 8(10), Article 1193. https://doi.org/10.3390/cells8101193
  29. Balusu, S., Van Wonterghem, E., De Rycke, R., Raemdonck, K., Stremersch, S., Gevaert, K., Brkic, M., Demeestere, D., Vanhooren, V., Hendrix, A., Libert, C., & Vandenbroucke, R. E. (2016). Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. Embo Molecular Medicine, 8(10), 1162-1183. https://doi.org/10.15252/emmm.201606271
  30. Wang, G. H., Dinkins, M., He, Q., Zhu, G., Poirier, C., Campbell, A., Mayer-Proschel, M., & Bieberich, E. (2012). Astrocytes Secrete Exosomes Enriched with Proapoptotic Ceramide and Prostate Apoptosis Response 4 (PAR-4) potential mechanism of apoptosis induction in Alzheimer disease (AD). Journal of Biological Chemistry, 287(25), 21384-21395. https://doi.org/10.1074/jbc.M112.340513
  31. Fader, C. M., & Colombo, M. I. (2009). Autophagy and multivesicular bodies: two closely related partners. Cell Death and Differentiation, 16(1), 70-78. https://doi.org/10.1038/cdd.2008.168
  32. Rusten, T. E., & Simonsen, A. (2008). ESCRT functions in autophagy and associated disease. Cell Cycle, 7(9), 1166-1172. https://doi.org/10.4161/cc.7.9.5784
  33. Meng, T., Lin, S., Zhuang, H., Huang, H., He, Z., Hu, Y., Gong, Q., & Feng, D. (2019). Recent progress in the role of autophagy in neurological diseases. Cell Stress, 3(5), 141–161. https://doi.org/10.15698/cst2019.05.186
  34. Banerjee, R., Beal, M. F., & Thomas, B. (2010). Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications. Trends in Neurosciences, 33(12), 541-549. https://doi.org/10.1016/j.tins.2010.09.001
  35. Guo, F., Liu, X. Y., Cai, H. B., & Le, W. D. (2018). Autophagy in neurodegenerative diseases: pathogenesis and therapy. Brain Pathology, 28(1), 3-13. https://doi.org/10.1111/bpa.12545
  36. Pascua-Maestro, R., Gonzalez, E., Lillo, C., Ganfornina, M. D., Falcon-Perez, J. M., & Sanchez, D. (2019). Extracellular Vesicles Secreted by Astroglial Cells Transport Apolipoprotein D to Neurons and Mediate Neuronal Survival Upon Oxidative Stress. Frontiers in Cellular Neuroscience, 12, Article 526. https://doi.org/10.3389/fncel.2018.00526
  37. Venturini, A., Passalacqua, M., Pelassa, S., Pastorino, F., Tedesco, M., Cortese, K., Gagliani, M. C., Leo, G., Maura, G., Guidolin, D., Agnati, L. F., Marcoli, M., & Cervetto, C. (2019). Exosomes From Astrocyte Processes: Signaling to Neurons. Frontiers in Pharmacology, 10, Article 1452. https://doi.org/10.3389/fphar.2019.01452
  38. Lafourcade, C., Ramirez, J. P., Luarte, A., Fernandez, A., & Wyneken, U. (2016). MiRNAs in Astrocyte-Derived Exosomes as Possible Mediators of Neuronal Plasticity. Journal of Experimental Neuroscience, 10, 1-9. https://doi.org/10.4137/jen.s39916
  39. Schiera, G., Di Liegro, C. M., & Di Liegro, I. (2020). Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles. International Journal of Molecular Sciences, 21(1), Article 266. https://doi.org/10.3390/ijms21010266
  40. Santello, M., Cali, C., & Bezzi, P. (2012). Gliotransmission and the Tripartite Synapse. Synaptic Plasticity: Dynamics, Development and Disease, 970, 307-331. https://doi.org/10.1007/978-3-7091-0932-8_14
  41. Durkee, C. A., & Araque, A. (2019). Diversity and Specificity of Astrocyte-neuron Communication. Neuroscience, 396, 73-78. https://doi.org/10.1016/j.neuroscience.2018.11.010
  42. Verkhratsky, A., & Nedergaard, M. (2014). Astroglial cradle in the life of the synapse. Philosophical Transactions of the Royal Society B-Biological Sciences, 369(1654), Article 20130595. https://doi.org/10.1098/rstb.2013.0595
  43. van Gool, W. A., van de Beek, D., & Eikelenboom, P. (2010). Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet, 375(9716), 773-775. https://doi.org/10.1016/s0140-6736(09)61158-2
  44. Bernardinelli, Y., Randall, J., Janett, E., Nikonenko, I., Konig, S., Jones, E. V., Flores, C. E., Murai, K. K., Bochet, C. G., Holtmaat, A., & Muller, D. (2014). Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability. Current Biology, 24(15), 1679-1688. https://doi.org/10.1016/j.cub.2014.06.025

Downloads

How to Cite

1.
Shuliatnikova TV, Shavrin VO. Ultrastructural features of astroglial endosomal system state in sepsis-associated encephalopathy. Pathologia [Internet]. 2020May25 [cited 2026May25];17(1). Available from: https://pat.zsmu.edu.ua/article/view/203742

Issue

Vol. 17 No. 1 (2020)

Section

Original research

License

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Лицензия Creative Commons