АСТРОЦИТЫ И ИХ РОЛЬ В ПАТОЛОГИИ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ

Определение структурно-функционального значения астроцитов в физиологии и патологии ЦНС является актуальной проблемой современной нейробиологии и клинической неврологии. Астроциты - глиальные клетки мозга, составляют мозговое вещество, поддерживают нейроны и разделяют их своими телами на компартменты. Они участвуют в иммунном ответе мозга, способны поддерживать хроническое воспаление и прогрессирующую нейродегенерацию, благодаря гиперэкспрессии цитокинов, факторов роста и хемокинов. В обзоре рассматриваются ключевые особенности астроглиоза, как комплекса молекулярных, клеточных и функциональных изменений астроцитов в ответ на различные повреждения мозга. Реактивный астроглиоз имеет решающее значение для регенерации и ремоделирования нейронных цепей после травмы и ишемии и может оказывать как положительное, так и негативное влияние. Индикатором активации астроцитов служит гиперэкспрессия белка S100b, который характерен для глиальных клеток и расположен преимущественно в астроцитах. При церебральной ишемии, черепно-мозговой травме или нейродегенеративных заболеваниях происходит модуляция астроглиоза, направленная на обеспечение механизмов репарации повреждённых отделов мозга, что определяет возможности поиска новых средств фармакологической коррекции активированных астроцитов и других компонентов глии для комплексной терапии неврологических заболеваний.

Heneka M.T., Rodriguez J.J., Verkhratsky A. Neuroglia in neurodegeneration. Brain Res Rev. 2010; 63: 189-211.

Sofroniew M.V., Vinters H.V. Astrocytes: biology and pathology. Acta Neuropathol. 2010; 119: 7-35.

Pekny M., Pekna M., Messing A., Steinhäuser C., Lee J.M., Parpura V., et al. Astrocytes: a central element in neurological diseases. Acta Neuropathol. 2016; 31(3): 323-45.

Vangilder R. L., Rosen C.L., Barr T. L., Huber J D. Targeting the neurovascular unit for treatment of neurological disorders. Pharmacol Ther. 2011; 130(3): 239-47.

von Bartheld C.S., Bahney J., Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol. 2016; 15; 524(18): 3865-95.

Azevedo F.A., Carvalho L.R., Grinberg L.T., Farfel J.M., Ferretti R.E., Leite R.E. et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009; 513: 532-41.

Butt A.M., Ransom B.R. Morphology of astrocytes and oligodendrocytes during development in the intact rat optic nerve. J Comp Neurol. 1993; 338(1): 141-58.

Benarroch E.E. Neuron-astrocyte interactions: partnership for normal function and disease in the central nervous system. Mayo Clin Proc. 2005; 80 (10): 1326-38.

Parpura V., Grubišić V., Verkhratsky A. Ca(2+) sources for the exocytotic release of glutamate from astrocytes. Biochim Biophys Acta. 2011; 1813(5): 984-91.

Powell E.M., Geller H.M. Dissection of astrocyte-mediated cues in neuronal guidance and process extension. Glia. 1999; 26: 73-83.

Nett W.J., Oloff S.H., McCarthy K.D. Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. J Neurophysiol. 2002; 87(1): 528-37.

Floyd C.L., Gorin F.A., Lyeth B.G. Mechanical Strain Injury Increases Intracellular Sodium and Reverses Na+/Ca2+ Exchange in Cortical Astrocytes. Glia. 2005; 51(1): 35-46.

Oh S.J., Lee C.J. Distribution and Function of the Bestrophin-1 (Best1) Channel in the Brain. Exp Neurobiol. 2017; 26(3): 113-21.

Larsen B.R., Stoica A., MacAulay N. Managing Brain Extracellular K+ during Neuronal Activity: The Physiological Role of the Na+/K+-ATPase Subunit Isoforms. Front Physiol. 2016; 7: 141.

Bellot-Saez A., Kékesi O., Morley J.W., Buskila Y. Astrocytic modulation of neuronal excitability through K+ spatial buffering. Neurosci Biobehav Rev. 2017; 77: 87-97.

Gordon GR, Mulligan SJ, MacVicar BA. Astrocyte control of the cerebrovasculature. Glia. 2007; 55(12): 1214-21.

Yu A., Salazar H., Plested A.J.R., Lau A.Y. Neurotransmitter Funneling Optimizes Glutamate Receptor Kinetics. Neuron. 2018; 97(1): 139-49.

Yu A, Lau AY. Energetics of Glutamate Binding to an Ionotropic Glutamate Receptor. J Phys Chem B. 2017; 121(46): 10436-42.

Zhou Q., Sheng M. NMDA receptors in nervous system diseases. Neuropharmacology. 2013; 74: 69-75.

Szczurowska E., Mareš P. NMDA and AMPA receptors: development and status epilepticus Physiol Res. 2013; 62 (Suppl 1): 21-38.

Lerma J. Kainate receptor physiology. Current Opinion in Pharmacology. 2006; 6: 89-97.

Traynelis S.F., Wollmuth L.P., McBain C.J., Menniti F.S., Vance K.M., Ogden K.K. et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010; 62(3): 405-96.

Dzamba D., Honsa P., Valny M., Kriska J., Valihrach L., Novosadova V. et al. Quantitative Analysis of Glutamate Receptors in Glial Cells from the Cortex of GFAP/EGFP Mice Following Ischemic Injury: Focus on NMDA Receptors. Cell Mol Neurobiol. 2015; 35(8): 1187-202.

Montes de Oca Balderas P., Aguilera P. A Metabotropic-Like Flux-Independent NMDA Receptor Regulates Ca2+ Exit from Endoplasmic Reticulum and Mitochondrial Membrane Potential in Cultured Astrocytes. PLoS One. 2015; 10(5):e0126314. doi:10.1371/journal.pone.0126314.

Pirttimaki T.M., Sims R.E., Saunders G., Antonio S.A., Codadu N.K., Parri H.R. Astrocyte-mediated neuronal synchronization properties revealed by false gliotransmitter release. J Neurosci. 2017; 37(41): 9859-70.

Loane D.J., Stoica B.A., Faden A.I. Metabotropic glutamate receptor-mediated signaling in neuroglia. Wiley Interdiscip Rev Membr Transp Signal. 2012; 1:136-150. doi:10.1002/wmts.30

Hathaway H.A., Pshenichkin S., Grajkowska E., Gelb T., Emery A.C., Wolfe B.B. et al., Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism. Neuropharmacology. 2015; 93: 199-208. doi: 10.1016/j.neuropharm.2015.02.007.

Gurevich V.V., Gurevich E.V. Overview of different mechanisms of arrestin-mediated signaling. Curr Protoc Pharmacol. 2014; 67: Unit 2.10.1-9. doi: 10.1002/0471141755.ph0210s67.

Dringen R. Metabolism and functions of glutathione in brain. Prog Neuro-biol. 2000; 62: 649-71.

Wilms H., Sievers J., Rickert U., Rostami-Yazdi M., Mrowietz U., Lucius R. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain in-flammation. J Neuroinflamm. 2010; 7: 30-7.

Argaw A.T., Asp L., Zhang J., Navrazhina K., Pham T., Mariani J.N. et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest. 2012; 122: 2454-68.

Almutairi M.M., Gong C., Xu Y.G., Chang Y., Shi H. Factors controlling permeability of the blood-brain barrier. Cell Mol Life Sci. 2016; 73(1): 57-77.

Mulder S.D., Veerhuis R., Blankenstein M.A., Nielsen H.M. The effect of amyloid associated proteins on the expression of genes involved in amyloid-β clearance by adult human astrocytes. Exp Neurol. 2012; 233(1): 373-9.

Surprenant A., North R.A. Signaling at purinergic P2X receptors. Annu Rev Physiol. 2009; 71: 333-59.

Alves L.A., da Silva J.H., Ferreira D.N., Fidalgo-Neto A.A., Teixeira P.C., de Souza C.A. et al. Structural and molecular modeling features of P2X receptors. Int J Mol Sci. 2014; 15(3): 4531-49.

Ballerini P., Rathbone M.P., Di Iorio P., Renzetti A., Giuliani P., D’Alimonte I. et al. Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release. Neuroreport. 1996; 7(15-17): 2533-7.

Hirayama Y., Ikeda-Matsuo Y., Notomi S., Enaida H., Kinouchi H., Koizumi S. Astrocyte-mediated ischemic tolerance. J Neurosci. 2015; 35(9): 3794-805.

Ye X., Shen T., Hu J., Zhang L., Zhang Y., Bao L. et al. Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse. Exp Neurol. 2017; 292: 46-55.

Kimbler D.E., Shields J., Yanasak N., Vender J.R., Dhandapani K.M. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice. PLoS One. 2012; 7(7):e41229. doi: 10.1371/journal.pone.0041229.

Chu K., Yin B., Wang J., Peng G., Liang H., Xu Z. et al. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus. J Neuroinflammation. 2012; 18; 9:69. doi: 10.1186/1742-2094-9-69.

Sperlágh B., Zsilla G., Baranyi M., Illes P., Vizi E.S. Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus. Neuroscience. 2007; 149(1): 99-111.

Franke H., Verkhratsky A., Burnstock G., Illes P. Pathophysiology of astroglial purinergic signalling. Purinergic Signal. 2012; 8(3): 629-57.

Sofroniew M.V. Astrogliosis. Cold Spring Harb Perspect Biol. 2015; 7(2): a020420. doi: 10.1101/cshperspect.a020420

Delbro D., Westerlund A., Björklund U., Hansson E. In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca2+ transients are attenuated due to interleukin-1β release and rearrangement of actin filaments. Neuroscience. 2009; 159: 770-9.

Chatterjee S., Sikdar S.K. Corticosterone treatment results in enhanced release of peptidergic vesicles in astrocytes via cytoskeletal rearrangements. Glia. 2013; 61: 2050-62.

Ryu H.J., Kim J.-E., Yeo S.-I., Kim D.-W., Kwon O.-S., Choi S.Y., Kang T.-C. F-actin depolymerization accelerates clasmatodendrosis via activation of lysosome-derived autophagicastroglial death. Brain Res. Bull. 2011; 85: 368-73.

Wagner D.C., Scheibe J., Glocke I., Weise G., Deten A., Boltze J., Kranz A. Object-based analysis of astroglial reaction and astrocyte subtype morphology after ischemic brain injury. Acta Neurobiol Exp (Wars). 2013; 73(1): 79-87.

Silver J., Miller J.H. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004; 5: 146-56.

Eng L.F., Ghirnikar R.S. GFAP and astrogliosis. Brain Pathol. 1994; 4(3): 229-37.

Wang P., Qin D., Wang Y.F. Oxytocin Rapidly Changes Astrocytic GFAP Plasticity by Differentially Modulating the Expressions of pERK 1/2 and Protein Kinase A. Front Mol Neurosci. 2017; 15; 10:262. doi: 10.3389/fnmol.2017.00262.

Zhao L., Burt A.D. The diffuse stellate cell system. J Mol Histol. 2007; 38: 53-64.

Steiner J., Bogerts B., Schroeter M., Bernstein H. S100B protein in neuro-degenerative disorders. Clin Chem Lab Med. 2011; 49(3): 409-24.

Mrak R.E., Griffin W.S. The role of activated astrocytes and of the neuro-trophic cytokine S100B in the pathogenesis of Alzheimer’s disease. Neurobiol. Aging. 2001; 22: 915-22.

Vignoli B., Canossa M. Glioactive ATP controls BDNF recycling in cortical astrocytes. Commun Integr Biol. 2017; 19; 10(1):e1277296. doi: 10.1080/19420889.2016.1277296.

Zhao Z., Alam S., Oppenheim R.W., Prevette D.M., Evenson A., Parsadanian A. Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy. Exp Neurol. 2004; 190: 356-72.

Sofroniew M.V. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009; 32(12): 638-47.

Xi G., Keep R.F., Hua Y., Xiang J., Hoff J.T. Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning. Stroke. 1999; 30: 1247-55.

Nicole O., Goldshmidt A., Hamill C.E., Sorensen S.D., Sastre A., Lyubos-lavsky P. et al. Activation of protease-activated receptor-1 triggers brain injury. J Neurosci. 2005; 25: 4319-29.

Danbolt N.C. Glutamate uptake. Prog Neurobiol. 2001; 65: 1-105.

McBean G.J. Cerebral cystine uptake: a tale of two transporters. Trends Pharmacol Sci. 2002; 23: 299-302.

D’Ambrosio R. The role of glial membrane ion channels in seizures and epileptogenesis. Pharmacol Ther. 2004; 103: 95-108.

Kasprowska D., Machnik G., Kost A., Gabryel B. Time-Dependent Changes in Apoptosis Upon Autophagy Inhibition in Astrocytes Exposed to Oxygen and Glucose Deprivation. Cell Mol Neurobiol. 2017; 37(2): 223-34.

Marconi R., De Fusco M., Aridon P., Plewnia K., Rossi M., Carapelli S. et al. Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23. Ann Neurol. 2003; 53: 376-81.

Montagna P. The physiopathology of migraine: the contribution of genetics. Neurol Sci. 2004; 25 (Suppl 3): 93-6.