ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2014-5-138-148ssmu-233Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESСТРУКТУРНАЯ И ФУНКЦИОНАЛЬНАЯ ГЕТЕРОГЕННОСТЬ АСТРОЦИТОВ ГОЛОВНОГО МОЗГА: РОЛЬ В НЕЙРОДЕГЕНЕРАЦИИ И НЕЙРОВОСПАЛЕНИИSTRUCTURAL AND FUNCTIONAL HETEROGENEITY OF ASTROCYTES IN THE BRAIN: ROLE IN NEURODEGENERATION AND NEUROINFLAMMATIONМоргунА. В.MorgunA. V.

Моргун Андрей Васильевич — кандидат медицинских наук

allasalmina@mail.ruМалиновскаяН. А.MalinovskayaN. A.

Малиновская Наталия Александровна — кандидат медицинских наук

allasalmina@mail.ruКомлеваЮ. К.KomlevaYu. K

Комлева Юлия Константиновна — кандидат медицинских наук

allasalmina@mail.ruЛопатинаО. Л.LopatinaO. L.

Лопатина Ольга Леонидовна — кандидат биологических наук

allasalmina@mail.ruКувачеваН. В.KuvachevaN. V.

Кувачева Наталья Валерьевна — кандидат фармацевтических наук

allasalmina@mail.ruПанинаЮ. А.PaninaYu. A.

Панина Юлия Анатольевна — аспирант

allasalmina@mail.ruТаранушенкоТ. Е.TaranushenkoT. Ye.

Таранушенко Татьяна Евгеньевна — доктор медицинских наук, профессор

allasalmina@mail.ruСолончукР. Ю.SolonchukYu. R.

Солончук Юлия Рудольфовна — кандидат медицинских наук

allasalmina@mail.ruСалминаА. Б.SalminaA. B.

Салмина Алла Борисовна - доктор медицинских наук, профессор, кафедра педиатрии Института последипломного образования

allasalmina@mail.ruКрасноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого, КрасноярскРоссияV.F. Voino-Yasenetsky Krasnoyarsk State Medical University, KrasnoyarskRussian Federation201428102014135138148Copyright © Моргун А.В., Малиновская Н.А., Комлева Ю.К., Лопатина О.Л., Кувачева Н.В., Панина Ю.А., Таранушенко Т.Е., Солончук Р.Ю., Салмина А.Б., 20142014Моргун А.В., Малиновская Н.А., Комлева Ю.К., Лопатина О.Л., Кувачева Н.В., Панина Ю.А., Таранушенко Т.Е., Солончук Р.Ю., Салмина А.Б.Morgun A.V., Malinovskaya N.A., Komleva Y.K., Lopatina O.L., Kuvacheva N.V., Panina Y.A., Taranushenko T.Y., Solonchuk Y.R., Salmina A.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/233

В настоящем обзоре литературы обсуждаются вопросы структурной и функциональной гетерогенности клеток астроглиальной природы головного мозга, лежащих в основе формирования и развития значительного числа физиологических и патологических процессов. Принадлежащие к разным субпопуляциям астроциты демонстрируют разную чувствительность к действию повреждающих факторов, по-разному участвуют в реализации реактивных реакций или локального иммунного ответа. Присущие астроцитам ключевые функции – нейрогенез, нейрон-астроглиальное метаболическое сопряжение, глиальный контроль локального кровотока – во многом определяются тем, какие из клеток астроглиальной природы их реализуют. Изменения, наблюдаемые на начальных этапах прогрессирования нейродегенеративных заболеваний и патологии, ассоциированной с нарушением развития головного мозга, показывают, что их важным компонентом являются значимые изменения структурных и функциональных свойств астроцитов, и поэтому направленная регуляция указанных клеточно-молекулярных событий может представлять собой действенную терапевтическую стратегию, в которой ключевые мишени – молекулы, экспрессируемые клетками астроглиальной природы.

The review covers the current concepts on structural and functional heterogeneity of brain astrocytes that serve for numerous (patho)physiological processes in the central nervous system. Astrocytes from various subpopulations demonstrate different sensitivity to the action of pathogenic factors, varied behaviors in reactive processes and within the local immune response. Key functions of astrocytes like neurogenesis, neuron-astroglia metabolic coupling, glial control of local blood flow greatly depend on the origin and characteristics of astroglial cells. Changes at the initial stages of neurodegeneration or in neurodevelopmental disorders are associated with significant alterations in astroglial structural and functional properties, thus suggesting new approaches to therapeutic strategies implementing astroglia-expressing molecules and targets for effective

астроглиягетерогенностьнейродегенерациянарушения развития мозганейрогенезнейровоспалениеastrogliaheterogeneityneurodegenerationneurodevelopmental diseasesneurogenesisneuroinflammationReferencesFreeman M.R. Neuron-Glia Signaling in Nervous System Development, Function, and Disease. URL: http://www.hhmi.org/research/ecs/freeman.html (accessed 14 March 2013).. Freeman M.R. Neuron-Glia Signaling in Nervous System Development, Function, and Disease. URL: http://www.hhmi. org/research/ecs/freeman.html (accessed 14 March 2013).Shaham S. Glia–Neuron Interactions in Nervous System Function and Development // Curr. Top. Dev. Biol. 2005. V. 69. P. 39–66.Shaham S. Glia–Neuron Interactions in Nervous System Function and Development. Curr. Top. Dev. Biol., 2005, vol. 69, pp. 39–66.МожаеваН., Алексеенко В.А., Казначеева Е.В., Киселев К.И., Мамин А.Г., Семенова С.Б. Ионные каналы, обеспечивающие рецептор-зависимый вход ионов кальция через плазматическую мембрану в невозбудимых клетках // Информац. бюл. РФФИ. 1996. Т. 4, № 4. С. 299.Mozhayeva G.N., Alekseenko V.A., Kaznacheeva E.V., Kiselev K.I., Mamin A.G., Semenova S.B. Ion channels providing receptor-induced Ca-influx through plasma membrane of nonexcitable cells. Informatsionny byulleten RFFI – Information. Bull. RFBR, 1996, vol. 4, no. 4, pp. 299 (in Russian).Brough D., Le Feuvre R.A., Wheeler R.D., Solovyova N., Hilfiker S., Rothwell N.J., Verkhratsky A. Ca2+ stores and Ca2+ entry differentially contribute to the release of IL-1 beta and IL-1 alpha from murine macrophages // J. Immunol. 2003. V. 170, № 6. P. 3029–3036.Brough D., Le Feuvre R.A., Wheeler R.D., Solovyova N., Hilfiker S., Rothwell N.J., Verkhratsky A. Ca2+ stores and Ca2+ entry differentially contribute to the release of IL-1 beta and IL-1 alpha from murine macrophages. J. Immunol., 2003, vol. 170, no. 6, pp. 3029–3036.Picello E., Pizzo P., Di Virgilio F. Chelation of cyto-plasmic Ca2+ increases plasma membrane permeability in murine macrophages // J. Biol. Chem. 1990. V. 265, № 10. P. 5635–5639.Picello E., Pizzo P., Di Virgilio F. Chelation of cytoplas-mic Ca2+ increases plasma membrane permeability in murine macrophages. J. Biol. Chem., 1990, vol. 265, no. 10, pp. 5635–5639.Germain N., Banda E., Grabel L. Embryonic stem cell neurogenesis and neural specification // J. Cell Biochem. 2010. V. 111, № 3. Р. 535–542.Germain N., Banda E., Grabel L. Embryonic stem cell neurogenesis and neural specification. J. Cell Biochem., 2010, vol. 111, no. 3, pp. 535–542.Verkhratsky A., Rodríguez J.J., Parpura V. Astroglia in neurological diseases // Future Neurol. 2013. V. 8, № 2. P. 149–158.Verkhratsky A., Rodríguez J.J., Parpura V. Astroglia in neurological diseases. Future Neurol., 2013, vol. 8, no. 2, pp. 149–158.Kahle M.P., Lee B., Pourmohamad T., Cunningham A., Su H., Kim H., Chen Y., McCulloch C.E., Barbaro N.M., Law-ton M.T., Young W.L., Bix G.J. Perlecan domain V is upregulated in human brain arteriovenous malformation and could mediate the vascular endothelial growth factor effect in lesional tissue // Neuroreport. 2012. V. 23, № 10. P. 627–630.Kahle M.P., Lee B., Pourmohamad T., Cunningham A., Su H., Kim H., Chen Y., McCulloch C.E., Barbaro N.M., Lawton M.T., Young W.L., Bix G.J. Perlecan domain V is upregulated in human brain arteriovenous malformation and could mediate the vascular endothelial growth factor effect in lesional tissue. Neuroreport, 2012, vol. 23, no. 10, pp. 627–630.Barry D.S., Pakan J.M., McDermott K.W. Radial glial cells: key organisers in CNS development // Int J Biochem Cell Biol. 2014. V. 46. P. 76–79.Barry D.S., Pakan J.M., McDermott K.W. Radial glial cells: key organisers in CNS development. Int. J. Biochem. Cell. Biol., 2014, vol. 46, pp. 76–79.Morrens J., Van Den Broeck W., Kempermann G. Glial cells in adult neurogenesis // Glia. 2012. V. 60, № 2. P. 159–174.Morrens J., Van Den Broeck W., Kempermann G. Glial cells in adult neurogenesis. Glia, 2012, vol. 60, no. 2, pp. 159–174.Emsley J.G., Macklis J.D. Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS // Neuron Glia Biol. 2006. V. 2, № 3. P. 175–186.Emsley J.G., Macklis J.D. Astroglial heterogeneity closely reflects the neuronal-defined anatomy of the adult murine CNS. Neuron Glia Biol., 2006, vol. 2, no. 3, pp. 175–186.Oberheim N.A., Goldman S.A., Nedergaard M. Heterogeneity of astrocytic form and function // Methods Mol Biol. 2012. V. 814. P. 23–45.Oberheim N.A., Goldman S.A., Nedergaard M. Heterogeneity of astrocytic form and function. Methods Mol. Biol., 2012, vol. 814, pp. 23–45.Torper O., Pfisterer U., Wolf D.A., Pereira M., Lau S., Jakobsson J., Björklund A., Grealish S., Parmar M. Generation of induced neurons via direct conversion in vivo // PNAS USA. 2013. V. 110, № 17. Р. 7038–7043.Torper O., Pfisterer U., Wolf D.A., Pereira M., Lau S., Jakobsson J., Björklund A., Grealish S., Parmar M. Generation of induced neurons via direct conversion in vivo. PNAS USA, 2013, vol. 110, no. 17, pp. 7038–7043.Rakic P. Neurogenesis in adult primates // Pr. Brain Res. 2002. V. 138. P. 125–187.Rakic P. Neurogenesis in adult primates. Pr. Brain Res., 2002, vol. 138, pp. 125–187.Rakic P. The radial edifice of cortical architecture: from neuronal silhouttes to genetic engineering // Br. Res. Rev. 2007. V. 55. P. 204–219.Rakic P. The radial edifice of cortical architecture: from neuronal silhouttes to genetic engineering. Br. Res. Rev., 2007, vol. 55, pp. 204–219.Cantini G., Pisati F., Pessina S., Finocchiaro G., Pelle-gatta S. Immunotherapy against the radial glia marker GLAST effectively triggers specific antitumor effectors without autoimmunity // Oncoimmunology. 2012. V. 1, № 6. P. 884–893.Cantini G., Pisati F., Pessina S., Finocchiaro G., Pellegatta S. Immunotherapy against the radial glia marker GLAST effectively triggers specific antitumor effectors without autoimmunity. Oncoimmunology, 2012, vol. 1, no. 6, pp. 884–893.Roybon L., Hjalt T., Stott S., Guillemot F., Li J.Y., Brundin P. Neurogenin2 Directs Granule Neuroblast Production and Amplification while NeuroD1 Specifies Neuronal Fate during Hippocampal Neurogenesis // PLoS ONE. 2009. V. 4. Р. e4779.Roybon L., Hjalt T., Stott S., Guillemot F., Li J.Y., Brundin P. Neurogenin2 Directs Granule Neuroblast Production and Amplification while NeuroD1 Specifies Neuronal Fate during Hippocampal Neurogenesis. PLoS ONE, 2009, vol. 4, p. e4779.Kunze A., Congreso M.R., Hartmann C., Wallraff-Beck A., Hüttmann K., Bedner P., Requardt R., Seifert G., Redecker C., Willecke K., Hofmann A., Pfeifer A., Theis M., Steinhäuser C. Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus // Proc. Natl. Acad. Sci. USA. 2009. V. 106, № 27. P. 11336–11341.Kunze A., Congreso M.R., Hartmann C., Wallraff-Beck A., Hüttmann K., Bedner P., Requardt R., Seifert G., Redecker C., Willecke K., Hofmann A., Pfeifer A., Theis M., Steinhäuser C. Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus. Proc. Natl. Acad. Sci. USA, 2009, vol. 106, no. 27, pp. 11336–11341.Bamba Y., Shofuda T., Kanematsu D., Nonaka M., Yamasaki M., Okano H., Kanemura Y. Differentiation, polarization, and migration of human induced pluripotent stem cell-derived neural progenitor cells co-cultured with a human glial cell line with radial glial-like characteristics // Biochem. Biophys. Res. Commun. 2014. V. 447, № 4. P. 683–688.Bamba Y., Shofuda T., Kanematsu D., Nonaka M., Yamasaki M., Okano H., Kanemura Y. Differentiation, polarization, and migration of human induced pluripotent stem cell-derived neural progenitor cells co-cultured with a human glial cell line with radial glial-like characteristics. Biochem. Biophys. Res. Commun., 2014, vol. 447, no. 4, pp. 683–688.Gubert F., Zaverucha-do-Valle C., Pimentel-Coelho P.M., Mendez-Otero R., Santiago M.F. Radial glia-like cells persist in the adult rat brain // Brain Res. 2009. V. 1258. P. 43–52.Gubert F., Zaverucha-do-Valle C., Pimentel-Coelho P.M., Mendez-Otero R., Santiago M.F. Radial glia-like cells persist in the adult rat brain. Brain Res., 2009, vol. 1258, pp. 43–52.Stewart P.A., Wiley M.J. Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: A study using quail-chick transplantation chimeras // Develop. Biol. 1981. V. 84. P. 183–192.Stewart P.A., Wiley M.J. Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: A study using quail-chick transplantation chimeras. Develop. Biol., 1981, vol. 84, pp. 183–192.Willis C.L., Leach L., Clarke G.J., Nolan C.C., Ray D.E. Reversible disruption of tight junction complexes in the rat blood-brain barrier, following transitory focal astrocyte loss // Glia. 2004. V. 48. Р. 1–13.Willis C.L., Leach L., Clarke G.J., Nolan C.C., Ray D.E. Reversible disruption of tight junction complexes in the rat blood-brain barrier, following transitory focal astrocyte loss. Glia, 2004, vol. 48, pp. 1–13.Krum J.M., Kenyon K.L., Rosenstein J.M. Expression of blood–brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin // Exp. Neurol. 1997. V. 146. Р. 33–45.Krum J.M., Kenyon K.L., Rosenstein J.M. Expression of blood–brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin. Exp. Neurol., 1997, vol. 146, pp. 33–45.Салмина А.Б., Инжутова А.И., Моргун А.В., Окунева О.С., Малиновская Н.А., Лопатина О.Л., Петрова М.М., Таранушенко Т.Е., Фурсов А.А., Кувачева Н.В. НАД+-конвер¬тирующие ферменты в клетках нейрональной и глиальной природы: СD38 как новая молекула-мишень для нейропротекции // Вестник РАМН. 2012. № 10. С. 29–37.Salmina A.B., Inzhutova A.I., Morgun A.V., Okuneva O.S., Malinovskaya N.A., Lopatina O.L., Petrova M.M., Taranushenko T.E., Fursov A.A., Kuvacheva N.V. NAD+-converting Enzymes in Neuronal and Glial Cells: CD38 as a Novel Target for Neuroprotection. Vestnik RAMN – Herald of the Russian Academy of Medical Sciences, 2012, no. 10, pp. 29–37 (in Russian).Abbott N.J. Astrocyte-endothelial interactions and blood-brain barrier permeability // J. Anat. 2002. V. 200. P. 629–638.Abbott N.J. Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat., 2002, vol. 200, pp. 629–638.Rubino E., Rainero I., Vaula G., Crasto F., Gravante E., Negro E., Brega F., Gallone S., Pinessi L. Investigating the genetic role of aquaporin4 gene in migraine // J. Headache Pain. 2009. V. 10, № 2. Р. 111–114.Rubino E., Rainero I., Vaula G., Crasto F., Gravante E., Negro E., Brega F., Gallone S., Pinessi L. Investigating the genetic role of aquaporin4 gene in migraine. J. Headache Pain, 2009, vol. 10, № 2. Р. 111–114.Takano T., Tian G.F., Peng W., Lou N., Libionka W., Han X., Nedergaard M. Astrocyte-mediated control of cerebral blood flow // Nat. Neurosci. 2006. V. 9, № 2. Р. 260–267.Takano T., Tian G.F., Peng W., Lou N., Libionka W., Han X., Nedergaard M. Astrocyte-mediated control of cerebral blood flow. Nat. Neurosci., 2006, vol. 9, no. 2, pp. 260–267.Halassa M.M., Fellin T., Takano H., Dong J.H., Haydon P.G. Synaptic islands defined by the territory of a single astrocyte // J. Neurosci. 2007. V. 27, № 24. P. 6473–6477.Halassa M.M., Fellin T., Takano H., Dong J.H., Haydon P.G. Synaptic islands defined by the territory of a single astrocyte. J. Neurosci., 2007, vol. 27, no. 24, pp. 6473–6477.Anderson M.F., Sims N.R. The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions // J. Neurochem. 2002. V. 81, № 3. P. 541–549.Anderson M.F., Sims N.R. The effects of focal ischemia and reperfusion on the glutathione content of mitochondria from rat brain subregions. J. Neurochem., 2002, vol. 81, no. 3, pp. 541–549.Ricci G., Volpi L., Pasquali L., Petrozzi L., Siciliano G. As-trocyte–neuron interactions in neurological disorders // J. Biol. Phys. 2009. V. 35. P. 317–336.Ricci G., Volpi L., Pasquali L., Petrozzi L., Siciliano G. Astrocyte–neuron interactions in neurological disorders. J. Biol. Phys., 2009, vol. 35, pp. 317–336.Papadopoulos M.C., Koumenis I.L., Dugan L.L., Giffard R.G. Vulnerability to glucose deprivation injury correlates with glutathione levels in astrocytes // Brain Res. 1997. V. 748, № 1–2. P. 151–156.Papadopoulos M.C., Koumenis I.L., Dugan L.L., Giffard R.G. Vulnerability to glucose deprivation injury correlates with glutathione levels in astrocytes. Brain Res., 1997, vol. 748, no. 1–2, pp. 151–156.Chen Y., Vartiainen N.E., Ying W., Chan P.H., Koistinaho J., Swanson R.A. Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism // J. Neurochem. 2001. V. 77, № 6. P. 1601–1610.Chen Y., Vartiainen N.E., Ying W., Chan P.H., Koistinaho J., Swanson R.A. Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J. Neurochem., 2001, vol. 77, no. 6, pp. 1601–1610.Salmina A.B., Petrova M.M., Taranushenko T.E., Proko-penko S.V., Malinovskaya N.A., Okuneva O.S., Inzhutova A.I., Morgun A.V., Fursov A.A. Alteration of neuron-glia interactions in neurodegeneration: molecular biomarkers and therapeutic strategy // Neurodegenerative Diseases – Processes, Prevention, Protection and Monitoring / ed. R.C.-C. Chang. Rijeka: InTech, 2011. P. 273–300.Salmina A.B., Petrova M.M., Taranushenko T.E., Proko-penko S.V., Malinovskaya N.A., Okuneva O.S., Inzhutova A.I., Morgun A.V., Fursov A.A. Alteration of neuron-glia interactions in neurodegeneration: molecular biomarkers and therapeutic strategy. Neurodegenerative Diseases – Processes, Prevention, Protection and Monitoring. Ed. R.C.-C. Chang. Rijeka, InTech Publ., 2011, pp. 273–300.Rodriguez J.J., Verkhratsky A. Neuroglial Roots of Neuro-degenerative Diseases? // Mol. Neurobiol. 2011. V. 43, № 2. P. 87–96.Rodriguez J.J., Verkhratsky A. Neuroglial Roots of Neuro-degenerative Diseases? Mol. Neurobiol., 2011, vol. 43, no. 2, pp. 87–96.Hamby M.E., Sofroniew M.V. Reactive astrocytes as thera-peutic targets for CNS disorders // Neurotherapeutics. 2010. V. 7, № 4. P. 494–506.Hamby M.E., Sofroniew M.V. Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics, 2010, vol. 7, no. 4, pp. 494–506.Anderson M.A., Ao Y., Sofroniew M.V. Heterogeneity of reactive astrocytes // Neurosci. Lett. 2014. V. 565. P. 23–29.Anderson M.A., Ao Y., Sofroniew M.V. Heterogeneity of reactive astrocytes. Neurosci. Lett., 2014, vol. 565, pp. 23–29.Levi G., Patrizio M. Astrocyte heterogeneity: endogenous amino acid levels and release evoked by non-N-methyl-D-aspartate receptor agonists and by potassium-induced swelling in type-1 and type-2 astrocytes // J. Neurochem. 1992. V. 58, № 5. P. 1943–1952.Levi G., Patrizio M. Astrocyte heterogeneity: endogenous amino acid levels and release evoked by non-N-methyl-D-aspartate receptor agonists and by potassium-induced swelling in type-1 and type-2 astrocytes. J. Neurochem., 1992, vol. 58, no. 5, pp. 1943–1952.Reynolds R., Herschkowitz N. Oligodendroglial and astroglial heterogeneity in mouse primary central nervous system culture as demonstrated by differences in GABA and D-aspartate transport and immunocytochemistry // Brain Res. 1987. V. 433, № 1. P. 13–25.Reynolds R., Herschkowitz N. Oligodendroglial and astroglial heterogeneity in mouse primary central nervous system culture as demonstrated by differences in GABA and D-aspartate transport and immunocytochemistry. Brain Res., 1987, vol. 433, no. 1, pp. 13–25.Zhang Y., Barres B.A. Astrocyte heterogeneity: an underappreciated topic in neurobiology // Curr. Opin. Neurobiol. 2010. V. 20, № 5. P. 588–594.Zhang Y., Barres B.A. Astrocyte heterogeneity: an underappreciated topic in neurobiology. Curr. Opin. Neurobiol., 2010, vol. 20, no. 5, pp. 588–594.García-Marqués J., López-Mascaraque L. Clonal identity determines astrocyte cortical heterogeneity // Cereb. Cor-tex. 2013. V. 23, № 6. P. 1463–1472.García-Marqués J., López-Mascaraque L. Clonal identity determines astrocyte cortical heterogeneity. Cereb. Cortex., 2013, vol. 23, no. 6, pp 1463–1472.Molofsky A.V., Glasgow S.M., Chaboub L.S., Tsai H.H., Murnen A.T., Kelley K.W., Fancy S.P., Yuen T.J., Madi-reddy L., Baranzini S., Deneen B., Rowitch D.H., Oldham M.C. Expression profiling of Aldh1l1-precursors in the de-veloping spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions // Glia. 2013. V. 61, № 9. P. 1518–1532.Molofsky A.V., Glasgow S.M., Chaboub L.S., Tsai H.H., Murnen A.T., Kelley K.W., Fancy S.P., Yuen T.J., Madireddy L., Baranzini S., Deneen B., Rowitch D.H., Oldham M.C. Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia, 2013, vol. 61, no. 9, pp. 1518–1532.Rodríguez J.J., Yeh C.Y., Terzieva S., Olabarria M., Kulijewicz-Nawrot M., Verkhratsky A. Complex and region-specific changes in astroglial markers in the aging brain // Neurobiol. Aging. 2014. V. 35, № 1. P. 15–23.Rodríguez J.J., Yeh C.Y., Terzieva S., Olabarria M., Kulijewicz-Nawrot M., Verkhratsky A. Complex and region-specific changes in astroglial markers in the aging brain. Neurobiol. Aging., 2014, vol. 35, no. 1, pp. 15–23.Mishima T., Hirase H. In vivo intracellular recording sug-gests that gray matter astrocytes in mature cerebral cortex and hippocampus are electrophysiologically homogeneous // J. Neurosci. 2010. V. 30, № 8. P. 3093–3100.Mishima T., Hirase H. In vivo intracellular recording sug-gests that gray matter astrocytes in mature cerebral cortex and hippocampus are electrophysiologically homogeneous. J. Neurosci., 2010, vol. 30, no. 8, pp. 3093–3100.Aerts J.T., Louis K.R., Crandall S.R., Govindaiah G., Cox C.L., Sweedler J.V. Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization // Anal. Chem. 2014. V. 86, № 6. P. 3203–3208.Aerts J.T., Louis K.R., Crandall S.R., Govindaiah G., Cox C.L., Sweedler J.V. Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization. Anal. Chem., 2014, vol. 86, no. 6, pp. 3203–3208.Krencik R., Weick J.P., Liu Y., Zhang Z.J., Zhang S.C. Specification of transplantable astroglial subtypes from human pluripotent stem cells // Nat. Biotechnol. 2011. V. 29, № 6. P. 528–534.Krencik R., Weick J.P., Liu Y., Zhang Z.J., Zhang S.C. Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat. Biotechnol., 2011, vol. 29, no. 6, pp. 528–534.Mele T., Jurič D.M. Identification and pharmacological characterization of the histamine H3 receptor in cultured rat astrocytes // Eur. J. Pharmacol. 2013. pii: S0014–2999(13)00785-1. doi: 10.1016/j.ejphar.2013.10.028. [Epub ahead of print].Mele T., Jurič D.M. Identification and pharmacological characterization of the histamine H3 receptor in cultured rat astrocytes. Eur. J. Pharmacol., 2013. pii: S0014–2999(13)00785-1. doi: 10.1016/j.ejphar.2013.10.028. [Epub ahead of print].Sosunov A.A., Wu X., Tsankova N.M., Guilfoyle E., McKhann G.M. 2nd, Goldman J.E. Phenotypic heterogeneity and plasticity of isocortical and hippocampal astrocytes in the human brain // J. Neurosci. 2014. V. 34, № 6. P. 2285–2298.Sosunov A.A., Wu X., Tsankova N.M., Guilfoyle E., McKhann G.M. 2nd, Goldman J.E. Phenotypic heterogeneity and plasticity of isocortical and hippocampal astrocytes in the human brain. J. Neurosci., 2014, vol. 34, no. 6, pp. 2285–2298.Салмина А.Б., Малиновская Н.А., Кувачева Н.В., Моргун А.В., Хилажева Е.Д., Горина Я.В., Пожиленкова Е.А., Фролова О.В. Коннексиновые и паннексиновые транспортные системы в клетках нейроваскулярной единицы головного мозга // Нейрохимия. 2014. T. 31, № 2. С. 122–133.Salmina A.B., Malinovskaya N.A., Kuvacheva N.V., Morgun A.V., Khilazheva E.D., Gorina Ya.V., Pozhilenkova E.A., Frolova O.V. Connexin and pannexin transport systems in the cells of brain neurovascular unit. Neyrochimia –Neurochemical Journal, 2014, vol. 31, no. 2, pp.122–133 (in Russian).Lundgaard I., Osório M.J., Kress B.T., Sanggaard S., Nedergaard M. White matter astrocytes in health and disease // Neuroscience. 2013. pii: S0306-4522(13)00903-2. doi: 10.1016/j.neuroscience.2013.10.050. [Epub ahead of print].Lundgaard I., Osório M.J., Kress B.T., Sanggaard S., Nedergaard M. White matter astrocytes in health and dis-ease. Neuroscience, 2013. pii: S0306-4522(13)00903-2. doi: 10.1016/j.neuroscience.2013.10.050. [Epub ahead of print].Ugbode C.I., Hirst W.D., Rattray M. Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes // J. Neurochem. 2014. doi: 10.1111/jnc.12759. [Epub ahead of print].Ugbode C.I., Hirst W.D., Rattray M. Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. J. Neurochem., 2014. doi: 10.1111/jnc.12759. [Epub ahead of print].Chaboub L.S., Deneen B. Developmental origins of astrocyte heterogeneity: the final frontier of CNS development // Dev Neurosci. 2012. V. 34, № 5. P. 379–388.Chaboub L.S., Deneen B. Developmental origins of astro-cyte heterogeneity: the final frontier of CNS development. Dev. Neurosci., 2012, vol. 34, no. 5, pp. 379–388.Lukaszevicz A.C., Sampaïo N., Guégan C., Benchoua A., Couriaud C., Chevalier E., Sola B., Lacombe P., Onté-niente B. High sensitivity of protoplasmic cortical astroglia to focal ischemia // J. Cereb. Blood. Flow. Metab. 2002. V. 22, № 3. P. 289–298.Lukaszevicz A.C., Sampaïo N., Guégan C., Benchoua A., Couriaud C., Chevalier E., Sola B., Lacombe P., Onténiente B. High sensitivity of protoplasmic cortical astroglia to focal ischemia. J. Cereb. Blood. Flow. Metab., 2002, vol. 22, no. 3, pp. 289–298.Fitting S., Zou S., Chen W., Vo P., Hauser K.F., Knapp P.E. Regional heterogeneity and diversity in cytokine and chemokine production by astroglia: differential responses to HIV-1 Tat, gp120, and morphine revealed by multiplex analysis // J. Proteome Res. 2010. V. 9, № 4. P. 1795–1804.Fitting S., Zou S., Chen W., Vo P., Hauser K.F., Knapp P.E. Regional heterogeneity and diversity in cytokine and chemokine production by astroglia: differential responses to HIV-1 Tat, gp120, and morphine revealed by multiplex analysis. J. Proteome Res., 2010, vol. 9, no. 4, pp. 1795–1804.Theodosis D.T., Poulain D.A., Oliet S.H.R. Activity-dependent structural and functional plasticity of astrocyte-neuron interactions // Physiol. Rev. 2008. V. 88, № 3. P. 983–1008.Theodosis D.T., Poulain D.A., Oliet S.H.R. Activity-dependent structural and functional plasticity of astrocyte-neuron interactions. Physiol. Rev., 2008, vol. 88, no. 3, pp. 983–1008.Morales I., Guzmán-Martínez L., Cerda-Troncoso C., Farías G.A., Maccioni R.B. Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches // Front Cell Neurosci. 2014. V. 8. P. 112.Morales I., Guzmán-Martínez L., Cerda-Troncoso C., Farías G.A., Maccioni R.B. Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci., 2014, vol. 8, pp. 112.Bushong E.A., Martone M.E., Jones Y.Z., Ellisman M.H. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains // J. Neurosci. 2002. V. 22, № 1. P. 183–192.Bushong E.A., Martone M.E., Jones Y.Z., Ellisman M.H. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci., 2002, vol. 22, no. 1, pp. 183–192.Giaume C., Koulakoff A., Roux L., Holcman D., Rouach N. Astroglial networks: a step further in neuroglial and gliovascular interactions // Nat. Rev. Neurosci. 2010. V. 11, № 2. P. 87–99.Giaume C., Koulakoff A., Roux L., Holcman D., Rouach N. Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat. Rev. Neurosci., 2010, vol. 11, no. 2, pp. 87–99.Sun D., Jakobs T.C. Structural remodeling of astrocytes in the injured CNS // Neuroscientist. 2012. V. 18, № 6. P. 567–588.Sun D., Jakobs T.C. Structural remodeling of astrocytes in the injured CNS. Neuroscientist, 2012, vol. 18, no. 6, pp. 567–588.Пискунов А.К. Биомаркеры нейровоспаления // Нейрохимия. 2010. Т. 27, № 1. С. 63–73.Piskunov A.K. Biomarkers neuroinflammation. Neyrochimia – Neurochemical Journal, 2010, vol. 27, no. 1, pp. 63–73 (in Russian).Kerschensteiner M., Gallmeier E., Behrens L., Leal V.V., Misgeld T., Klinkert W.E., Kolbeck R., Hoppe E., Oropeza-Wekerle R.L., Bartke I., Stadelmann C., Lassmann H., Wekerle H., Hohlfeld R. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? // J. Exp. Med. 1999. V. 189, № 5. P. 865–870.Kerschensteiner M., Gallmeier E., Behrens L., Leal V.V., Misgeld T., Klinkert W.E., Kolbeck R., Hoppe E., Oropeza-Wekerle R.L., Bartke I., Stadelmann C., Lassmann H., Wekerle H., Hohlfeld R. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J. Exp. Med., 1999, vol. 189, no. 5, pp. 865–870.Carpentier P.A., Begolka W.S., Olson J.K., Elhofy A., Karpus W.J., Miller S.D. Differential activation of astro-cytes by innate and adaptive immune stimuli // Glia. 2005. V. 49. P. 360–374.Carpentier P.A., Begolka W.S., Olson J.K., Elhofy A., Karpus W.J., Miller S.D. Differential activation of astrocytes by innate and adaptive immune stimuli. Glia, 2005, vol. 49, pp. 360–374.Griffiths M., Neal J.W., Gasque P. Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins // Int. Rev. Neurobiol. 2007. V. 82. P. 29–55.Griffiths M., Neal J.W., Gasque P. Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int. Rev. Neurobiol., 2007, vol. 82, pp. 29–55.Karpuk N., Burkovetskaya M., Fritz T., Angle A., Kielian T. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity // J. Neurosci. 2011. V. 31, № 2. P. 414–425.Karpuk N., Burkovetskaya M., Fritz T., Angle A., Kielian T. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. J. Neurosci., 2011, vol. 31, no. 2, pp. 414–425.Karpuk N., Burkovetskaya M., Kielian T. Neuroinflamma-tion alters voltage-dependent conductance in striatal astro-cytes // J. Neurophysiol. 2012. V. 108, № 1. P. 112–123.Karpuk N., Burkovetskaya M., Kielian T. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes. J. Neurophysiol., 2012, vol. 108, no. 1, pp. 112–123.Krencik R., Ullian E.M. A cellular star atlas: using astro-cytes from human pluripotent stem cells for disease studies // Front Cell Neurosci. 2013. V. 7. P. 25.Krencik R., Ullian E.M. A cellular star atlas: using astro-cytes from human pluripotent stem cells for disease studies. Front Cell Neurosci., 2013, vol. 7, pp. 25.

The authors declare that there are no conflicts of interest present.