Клеточные модели заболеваний нервной системы

Leonid G. Khaspekov1
1ФГБНУ «Научный центр неврологии», Москва, Россия

Аннотация


Клеточные модели являются важнейшим исследовательским инструментом в современной нейробиологии. Представленный обзор отечественной и зарубежной литературы обобщает основные данные экспериментальных исследований последних 15 лет, направленных на моделирование in vitro острых и хронических форм церебральной патологии с целью выяснения механизмов их патогенеза и поиска способов их фармакологической коррекции. Представлены результаты моделирования ишемических нейродеструктивных процессов, эпилепсии, болезней Паркинсона, Альцгеймера, Гентингтона, полученные с использованием современных клеточных методов исследования, таких как культивирование клеток в мультиэлектродной системе и технология индуцированных плюрипотентных стволовых клеток. Ряд ключевых положений по данной проблеме проиллюстрирован собственными приоритетными результатами автора и его лаборатории. Сформулированы ближайшие цели и перспективы исследований in vitro патогенетических механизмов заболеваний нервной системы и поиска новых нейропротекторов.

Литература

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Ключевые слова

культура клеток нервной системы; моделирование неврологических заболеваний; нейропротекция; современные клеточные технологии

Полный текст:

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Литература

Panula P., Rechardt L. The development of histochemically demonstrable cholinesterases in the rat neostriatum in vivo and in vitro. Histochemistry 1979; 64: 35–50. PMID: 521314.

Berger B., Di Porzio U., Dagnet M.C. Long-term development of mesencephalic dopaminergic neurons of mouse embryos in dissociated primary cultures: morphological and histochemical characteristics. Neuroscience 1982; 7: 193–205. PMID: 6123092.

Victorov I.V. Razvitiye i plastichnost’ neyronov v tkanevykh i kletochnykh kul’turakh. Dis. ... dokt. biol. nauk. [The development and plastisicity of neurons in tissue and cell cultures. D.Sci.(Biol.) diss.]. Мoscow. 1987. (In Russ.)

Sommer S.J. Ischemic stroke: experimental models and reality. Acta Neuropathol 2017; 133: 245–261. DOI: 10.1007/s00401-017-1667-0. PMID: 28064357.

Holloway P.M., Gavins F.N. Modeling ischemic stroke in vitro: status quo and future perspectives. Stroke 2016; 47: 561-569. DOI: 10.1161/STROKEAHA. 115.011932.

Choi D.W., Maulucci-Gedde M., Kriegstein A.R. Glutamate neurotoxicity in cortical cell culture. J Neurosci 1987; 7: 357–368. PMID: 2880937.

Huang R., Sochoka E., Hertz L. Cell culture studies of the role of elevated extracellular glutamate and K+ in neuronal cell death during and after anoxia/ ischemia. Neurosci Behav Rev 1997; 21: 129–134. PMID: 9062935.

Khodorov B. Glutamate induced deregulation of calcium homeostasis and mitochondrial

disfunction in mammalian central neurones. Prog Biophys Mol Biol 2004; 2: 279–351. PMID: 15288761.

Surin A.M. Mekhanizmy disfunktsii mitokhondriy i narusheniy ionnogo gomeostaza pri glutamatnoy neyrotoksichnosti: Dis. … dokt. biol. nauk. [Mechanisms of mitochondrial disfunction and ion homeostasis disturbances as consequences of glutamate neurotoxicity. D.Sci.(Biol.) diss.]. Мoscow. 2014. (In Russ.)

Woodruff T.M., Thundyil J., Tang S.-C. et al. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol Neurodegener 2011; 6: 11. DOI: 10.1186/1750-1326-6-11. PMID: 21266064.

Stelmashook E.V., Isaev N.K., Lozier E.R. et al. Role of glutamine in neuronal survival and death during brain ischemia and hypoglycemia. Int J Neurosci 2011; 121: 415–422. DOI: 10.3109/00207454.2011.570464. PMID: 21574892.

Stelmashook E.V., Isaev N.K., Plotnikov E.Y. et al. Effect of transitory glucose deprivation on mitochondrial structure and functions in cultured cerebellar granule neurons. Neurosci Lett 2009; 461: 140-144. DOI: 10.1016/j. neulet.2009.05.073. PMID: 19500653.

Stelmashook E.V., Isaev N.K., Zorov D.B. Paraquat potentiates glutamate toxicity in immature cultures of cerebellar granule neurons. Toxicol Lett 2007; 174: 82–88. DOI: 10.1016/j.toxlet. 2007.08.012. PMID: 17919854.

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Isaev N.K., Lozier E.R., Novikova S.V. et al. Glucose starvation stimulates Zn2+ toxicity in cultures of cerebellar granule neurons. Brain Res Bull 2012; 87: 80-84. DOI: 10.1016/ j.brainresbull.2011.10.017. PMID: 2207950377

Losier E.R., Stelmashook E.V., Uzbekov R.E. et al. Stimulation of kainite toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process. Toxicol Lett 2012; 208: 36-40. DOI: 10.1016/j. toxlet.2011.10.003. PMID: 22008730.

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Shimono K., Baudry M., Panchenko V., Taketani M. Chronic multichannel recordings from organotypic hippocampal slice cultures: protection from excitotoxic effects of NMDA by noncompetitive NMDA antagonists. J Neurosci Meth 2002; 120: 193–202. PMID: 12385769.

Wahl A.-S., Buchthal B., Rode F. Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors. Neuroscience 2009; 158: 344–352. DOI: 10.1016/j.neuroscience.2008.06.018. PMID: 18616968.

Linke S., Goertz P., Baader S.L. et al. Aldolase C/Zebrin II is released to the extracellular space after stroke and inhibits the network activity of cortical neurons. Neurochem Res 2006; 31: 1297–1303. DOI: 10.1007/s11064-006-9169-9. PMID: 17053973.

Vishwakarma S.K., Bardia A., Tiwari S.K. et al. Current concept in neural regeneration research: NSCs isolation, characterization and transplantation in various neurodegenerative diseases and stroke: a review. J Adv Res 2014; 5: 277–294. DOI: 10.1016/j.jare.2013.04.005. PMID: 25685495.

DeLorenzo R.J., Sun D.A., Blair R.E., Sombati S. An in vitro model of stroke-induced epilepsy: elucidation of the roles of glutamate and calcium in the induction and maintenance of stroke-induced epileptogenesis. Int Rev Neurobiol 2007; 81: 59–84. DOI: 10.1016/S0074-7742(06) 81005-6. PMID: 17433918.

Noraberg J., Poulsen F.R., Blaabjerg M. et al. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair. Curr Drug Targets CNS Neurol Disord 2005; 4: 435-452. PMID: 16101559.

Jones N.A., Hill A.J., Smith I. et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharm Exp Ther 2010; 332: 569–577. DOI: 10.1124/ jpet.109.159145. PMID: 19906779.

Sun D.A., Sombati S., Blair R.E., DeLorenzo R.J. Long-lasting alterations in neuronal calcium homeostasis in an in vitro model of stroke induced epilepsy. Cell Calcium 2004; 35: 155–163. PMID: 14706289.

Corti S., Faravelli I., Cardano M., Conti L. Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery. Expert Opin Drug Discov 2015; 10: 615–629. DOI: 10.1517/17460441.2015.1037737. PMID: 25891144.

Tonges L., Frank T., Tatenhorst L. et al. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson’s disease. Brain 2012; 135: 3355–3370. DOI: 10.1093/brain/aws254. PMID: 23087045.

Desplats P., Lee H.J., Bae E.J. et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA

; 106: 13010–13015. DOI: 10.1073/pnas.0903691106. PMID: 19651612.

Hargus G., Cooper O., Deleidi M. et al. Differentiated parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in parkinsonian rats. Proc Natl Acad Sci USA 2010; 107:15921–15926. DOI: 10.1073/pnas. 1010209107. PMID: 20798034.

Hargus G., Ehrlich M., Hallmann A.-L., Kuhlmann T. Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development. Acta Neuropathol 2014; 127: 151–173. DOI: 10.1007/s00401-013-1222-6. PMID: 24306942.

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(In Russ.)

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evaluation of the results of neurotransplantation in experimental parkisonism]. Annals of Clinical and Experim Neurol 2015; 2: 28–32. (In Russ.)

Konovalova E.V., Lopacheva O.M., Grivennikov I.A. et al. Mutations in the Parkinson’s disease-associated PARK2 gene are accompanied by imbalance in programmed cell death Systems. Acta Naturae 2015; 7: 146-149. PMID: 26798503.

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; 9: 115. DOI: 10.1186/ 742-2094-9-115. PMID: 22651808.

Varghese K., Molnar P., Das M. et al. A new target for amyloid beta toxicity validated by standard and high-throughput electrophysiology. PLoS One 2010; 5: e8643. DOI: 10.1371/ journal.pone.0008643. PMID: 20062810.

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DOI: http://dx.doi.org/10.25692/ACEN.2018.5.9