Development of neuroprotection approaches for long-term space missions
Heading:
| 1Pastukhov, AO, 1Krisanova, NV, 1Pozdnyakova, NG, 1Borysov, AA, 1Sivko, RV, 1Nazarova, AG, 1Kalynovska, LM, 1Borisova, TO 1Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, Kyiv, Ukraine |
| Space Sci. & Technol. 2022, 28 ;(6):52-62 |
| https://doi.org/10.15407/knit2022.06.052 |
| Publication Language: Ukrainian |
Abstract: The aim of the study was to develop a strategy and methodology for neuroprotection during long-term space missions, which is based on a comprehensive study of the impact of therapeutic hypothermia combined with the action of neuroactive drugs on the key characteristics of synaptic transmission in brain nerve terminals, which change under the influence of planetary dust and under conditions of altered gravity. Development of neurotoxicity under conditions of altered gravity may result from excess extracellular glutamate, which causes by the reverse functioning of glutamate transporters. Under conditions of moderate and deep hypothermia, a gradual decrease in transporter-mediated release of L-[14C]glutamate from nerve terminals stimulated by plasma membrane depolarization with KCl and dissipation of the proton gradient of synaptic vesicles by the protonophore FCCP was demonstrated. This fact indicates a neuroprotective effect, which increases when hypothermia changes from moderate to deep. The possible risks of using hypothermia in space medicine have been determined. Hypothermia is not able to reduce the extracellular level of L-[14C]glutamate and [3H]GABA, which increase under the conditions of exposure to carbon-containing planetary dust. Hypothermia can lead to a further decrease in the rate of accumulation of neurotransmitters in the presence of carbon-containing planetary dust and contribute to the development of neurotoxicity, which is a possible risk of using hypothermia in space medicine. In this context, it is important to choose the optimal individual temperature regime for each astronaut.
|
| Keywords: brain nerve terminals, hypothermia, L-[14C]glutamate, planetary dust, synaptosomes, [3H]GABA |
References:
1. Borisova T. (2018). Nervous System Injury in Response to Contact With Environmental, Engineered and Planetary Micro- and Nano-Sized Particles Front. Physiol. V.9, P. 728.
https://doi.org/10.3389/fphys.2018.00728
2. Borisova T. (2019). Express assessment of neurotoxicity of particles of planetary and interstellar dust npj Microgravity. V.5, № 1, P. 2.
https://doi.org/10.1038/s41526-019-0062-7
3. Borisova T. (2022). Environmental Nanoparticles: Focus on Multipollutant Strategy for Environmental Quality and Health Risk Estimations Biomed. Nanomater. P. 305-321.
https://doi.org/10.1007/978-3-030-76235-3_11
4. Borisova T.A., Himmelreich N.H. (2005). Centrifuge-induced hypergravity: [3H]GABA and l-[14C]glutamate uptake, exocytosis and efflux mediated by high-affinity, sodium-dependent transporters Adv. Sp. Res. V.36, № 7, P. 1340-1345.
https://doi.org/10.1016/j.asr.2005.10.007
5. Borisova T.A., Krisanova N.V. (2008). Presynaptic transporter-mediated release of glutamate evoked by the protonophore FCCP increases under altered gravity conditions Adv. Sp. Res. V.42, № 12, P. 1971-1979.
https://doi.org/10.1016/j.asr.2008.04.012
6. Borisova T., Krisanova N., Himmelreich N. (2004). Exposure of animals to artificial gravity conditions leads to the alteration of the glutamate release from rat cerebral hemispheres nerve terminals Adv. Sp. Res. V.33, № 8, P. 1362-1367.
https://doi.org/10.1016/j.asr.2003.09.039
7. Borisova T., Krisanova N., Sivko R., et al. (2010). Cholesterol depletion attenuates tonic release but increases the ambient level of glutamate in rat brain synaptosomes Neurochem. Int. V.56, № 3, P. 466-478.
https://doi.org/10.1016/j.neuint.2009.12.006
8. Borisova T., Pozdnyakova N., Dudarenko M., et al. (2021). GABAA receptor agonist cinazepam and its active metabolite 3-hydroxyphenazepam act differently at the presynaptic site Eur. Neuropsychopharmacol. V.45, P. 39-51.
https://doi.org/10.1016/j.euroneuro.2021.03.013
9. Borisova T., Pozdnyakova N., Krisanova N., et al. (2021). Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals Food Chem. Toxicol. V.149, P. 112004.
https://doi.org/10.1016/j.fct.2021.112004
10. Borysov A., Pozdnyakova N., Pastukhov A., et al. (2018). Comparative analysis of neurotoxic potential of synthesized, native, and physiological nanoparticles Neuromethods. V.135, P. 203-227.
https://doi.org/10.1007/978-1-4939-7584-6_13/COVER
11. Borysov A., Tarasenko A., Krisanova N., et al. (2020). Plastic smoke aerosol: Nano-sized particle distribution, absorption/fluorescent properties, dysregulation of oxidative processes and synaptic transmission in rat brain nerve terminals Environ. Pollut. V.263, P. 114502.
https://doi.org/10.1016/j.envpol.2020.114502
12. Cotman C.W. (1974). Isolation of synaptosomal and synaptic plasma membrane fractions. Methods Enzymol. V.31, P. 445-452.
https://doi.org/10.1016/0076-6879(74)31050-6
13. Fukunaga H. (2020). The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel? Int. J. Mol. Sci. V.21, № 17, P. 6349.
https://doi.org/10.3390/ijms21176349
14. Gaier J.R. (2005). The Effects of Lunar Dust on EVA Systems During the Apollo Missions.
15. Hupfeld K.E., McGregor H.R., Reuter-Lorenz P.A., et al. (2021). Microgravity effects on the human brain and behavior: Dysfunction and adaptive plasticity Neurosci. Biobehav. Rev. V.122, P. 176-189.
https://doi.org/10.1016/j.neubiorev.2020.11.017
16. Kammersgaard L.P., Jørgensen H.S., Rungby J.A., et al. (2002). Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study. Stroke. V.33, № 7, P. 1759-62.
https://doi.org/10.1161/01.STR.0000019910.90280.F1
17. Krisanova N., Kasatkina L., Sivko R., et al. (2013). Neurotoxic Potential of Lunar and Martian Dust: Influence on Em, Proton Gradient, Active Transport, and Binding of Glutamate in Rat Brain Nerve Terminals Astrobiology. V.13, № 8, P. 679-692.
https://doi.org/10.1089/ast.2012.0950
18. Krisanova N., Pozdnyakova N., Pastukhov A., et al. (2019). Vitamin D3 deficiency in puberty rats causes presynaptic malfunctioning through alterations in exocytotic release and uptake of glutamate/GABA and expression of EAAC-1/GAT-3 transporters Food Chem. Toxicol. V.123,
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.
https://doi.org/10.1016/j.neuint.2009.07.003
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
21. Larson E., Howlett B., Jagendorf A. (1986). Artificial reductant enhancement of the Lowry method for protein determination. Anal. Biochem. V.155, № 2, P. 243-248.
https://doi.org/10.1016/0003-2697(86)90432-X
22. Latch J.N., Hamilton R.F., Holian A., et al. (2008). Toxicity of lunar and martian dust simulants to alveolar macrophages isolated from human volunteers Inhal. Toxicol. V.20, № 2, P. 157-165.
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
24. Nordeen C.A., Martin S.L. (2019). Engineering Human Stasis for Long-Duration Spaceflight Physiology. V.34, № 2, P. 101-111.
https://doi.org/10.1152/physiol.00046.2018
25. Oberdörster G., Elder A., Rinderknecht A. (2009). Nanoparticles and the brain: cause for concern? J. Nanosci. Nanotechnol. V.9, № 8, P. 4996-5007.
https://doi.org/10.1166/jnn.2009.GR02
26. Oberdörster G., Oberdörster E., Oberdörster J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. V.113, № 7, P. 823-39.
https://doi.org/10.1289/ehp.7339
27. Paliienko K., Pastukhov A., Babič M., et al. (2020). Transient coating of γ-Fe 2 O 3 nanoparticles with glutamate for its delivery to and removal from brain nerve terminals Beilstein J. Nanotechnol. V.11, № 1, P. 1381-1393.
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