Розроблення підходів нейропротекції при довготривалих космічних місіях
Рубрика:
| Пастухов, АО, Крисанова, НВ, Позднякова, НГ, Борисов, АА, Сівко, РВ, Назарова, АГ, Каліновська, ЛМ, Борисова, ТО |
| Косм. наука технол. 2022, 28 ;(6):52-62 |
| https://doi.org/10.15407/knit2022.06.052 |
| Мова публікації: Українська |
Анотація: Мета роботи полягала у розробленні стратегії та методології нейропротекції при довготривалих космічних місіях, яка базується на комплексному дослідженні впливу терапевтичної гіпотермії, поєднаної з дією нейроактивних препаратів, на ключові характеристики синаптичної передачі у нервових терміналях головного мозку, що змінюються за дії планетарного пилу та за умов зміненої гравітації. Розвиток нейротоксичності за умов зміненої гравітації може бути зумовлений надлишковим позаклітинним глутаматом, що виникає, як результат реверсного функціонування глутаматних транспортерів. За умов зміни гіпотермії від помірної до глибокої, було продемонстровано поступове зниження транспортер-опосередкованого вивільнення L-[14C]глутамату стимульованого деполяризацією плазматичної мембрани KCl та дисипацією протонного градієнта синаптичних везикул протонофором FCCP. Цей факт свідчить про нейропротекторний ефект, який збільшується за умов зміни гіпотермії від помірної до глибокої. Визначені можливі ризики використання гіпотермії у космічній медицині. Гіпотермія не здатна знизити позаклітинний рівень L-[14C]глутамату та [3Н]ГАМК, що збільшуються за умов впливу карбон-вмісного планетарного пилу. Гіпотермія може призвести до подальшого зниження швидкості накопичення нейромедіаторів за умов присутності карбон-вмісного планетарного пилу та сприяти розвитку нейротоксичності, що є можливим ризиком використання гіпотермії у космічній медицині. У цьому контексті важливим є вибір оптимального індивідуального температурного режиму для кожного астронавту.
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| Ключові слова: L-[14С]глутамат, [3Н]γ-аміномасляна кислота, гіпотермія, нервові терміналі головного мозку, планетарний пил, синаптосоми |
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https://doi.org/10.1016/j.asr.2005.10.007
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https://doi.org/10.1016/j.asr.2008.04.012
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https://doi.org/10.1016/j.fct.2021.112004
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https://doi.org/10.3390/ijms21176349
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https://doi.org/10.1161/01.STR.0000019910.90280.F1
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https://doi.org/10.1016/j.fct.2018.10.054
19. Krisanova N. V., Trikash I.O., Borisova T.A. (2009). Synaptopathy under conditions of altered gravity: changes in synaptic vesicle fusion and glutamate release Neurochem. Int. V.55, № 8, P. 724-731.
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20. Lam C.W., Scully R.R., Zhang Y., et al. (2013). Toxicity of lunar dust assessed in inhalation-exposed rats Inhal. Toxicol. V.25, № 12, P. 661-678.
https://doi.org/10.3109/08958378.2013.833660
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https://doi.org/10.1016/0003-2697(86)90432-X
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https://doi.org/10.1080/08958370701821219
23. Mrozek S., Vardon F., Geeraerts T. (2012). Brain temperature: Physiology and pathophysiology after brain injury Anesthesiol. Res. Pract. V.2012, P. 989487.
https://doi.org/10.1155/2012/989487
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https://doi.org/10.1152/physiol.00046.2018
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https://doi.org/10.3762/bjnano.11.122
28. Pastukhov A., Borisova T. (2018). Levetiracetam-mediated improvement of decreased NMDA-induced glutamate release from nerve terminals during hypothermia Brain Res. V.1699,
https://doi.org/10.1016/j.brainres.2018.06.032
29. Pastukhov A., Borisova T. (2018). Combined Application of Glutamate Transporter Inhibitors and Hypothermia Discriminates Principal Constituent Processes Involved in Glutamate Homo- and Heteroexchange in Brain Nerve Terminals Ther. Hypothermia Temp. Manag. V.8, № 3, P. 143-149.
https://doi.org/10.1089/ther.2017.0047
30. Pastukhov A., Krisanova N., Pyrshev K., et al. (2020). Dual benefit of combined neuroprotection: Cholesterol depletion restores membrane microviscosity but not lipid order and enhances neuroprotective action of hypothermia in rat cortex nerve terminals Biochim. Biophys. Acta - Biomembr. V.1862, № 9, P. 183362.
https://doi.org/10.1016/j.bbamem.2020.183362
31. Patsula V., Borisova T., Kostiv U., et al. (2019). Effect of Fe3O4 @ SiO2 Nanoparticle Diameter on Glutamate Transport in Brain Nerve Terminals Nanosci. Nanotechnol. Lett. V.11, № 1, P. 61-69.
https://doi.org/10.1166/nnl.2019.2853
32. Pozdnyakova N., Borisova T. (2018). Evaluation of the neurotoxicity of the inorganic analogue of Martian dust enriched with the new carbon nanoparticles Sp. Res. Ukr. 2016 - 2018. P. 62-65.
33. Pozdnyakova N., Dudarenko M., Borisova T. (2019). Age-Dependency of Levetiracetam Effects on Exocytotic GABA Release from Nerve Terminals in the Hippocampus and Cortex in Norm and After Perinatal Hypoxia Cell. Mol. Neurobiol. V.39, № 5, P. 701-714.
https://doi.org/10.1007/s10571-019-00676-6
34. Pozdnyakova N.G., Pastukhov A.O., Dudarenko M.V., et al. (2018). Enrichment of the inorganic analogue of martian dust with the novel carbon nanoparticles obtained during combustion of carbohydrates and assesment of its meurotoxicity Space Sci. Technol. V.24, № 2, P. 60-71.
https://doi.org/10.15407/knit2018.02.060
35. Pozdnyakova N., Pastukhov A., Dudarenko M., et al. (2017). Enrichment of Inorganic Martian Dust Simulant with Carbon Component can Provoke Neurotoxicity Microgravity Sci. Technol.
https://doi.org/10.1007/s12217-016-9533-6
36. Scully R.R., Lam C.W., James J.T. (2013). Estimating safe human exposure levels for lunar dust using benchmark dose modeling of data from inhalation studies in rats Inhal. Toxicol. V.25, № 14, P. 785-793.
https://doi.org/10.3109/08958378.2013.849315
37. Tarasenko A.S., Sivko R. V., Krisanova N. V., et al. (2010). Cholesterol depletion from the plasma membrane impairs proton and glutamate storage in synaptic vesicles of nerve terminals J. Mol. Neurosci. V.41, № 3, P. 358-367.
https://doi.org/10.1007/s12031-010-9351-z