Analysis of biomodulatory properties and neurotoxicity of lunar dust analogue

1Nazarova, AG, 1Pozdnyakova, NG, 1Voronova, OO, 1Chunihin, OYu., 1Piskova, MV, 1Pastukhov, AO, 1Borysov, AA, 1Krisanova, NV, 1Borisova, TO
1Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, Kyiv, Ukraine
Kosm. nauka tehnol. 2015, 21 ;(4):103–111
Publication Language: Ukrainian

During inhalation, nano-/microsized particles of lunar dust are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of lunar dust has not yet been assessed. The research was focused on the analysis of the effects of lunar dust analogue on the key characteristics of glutamatergic neurotransmission. Disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The average size of particles of lunar dust analogue (JSC-1a, Lunar Soil Simulant, Orbitec, USA) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled L-[14C]glutamate, it was shown that there is an increase in L-[14C]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Na+] media in the presence of lunar dust analogue that led to an apparent increase in the initial velocity of L-[14C]glutamate uptake by 10 % in control rats, and those underwent to gravitational overload. Thus, the unique effect of lunar dust analogue to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on the extracellular glutamate homeostasis in the central nervous system that is extremely important for proper synaptic transmission. During a long-term mission, a combination of constant irritation due to dust particles, inflammation, stress, low gravity and microgravity, radiation, UV, and so on may consequently change the effects of the dust and                                    

aggravate neurological consequences. 

Keywords: lunar soil simulant; glutamate transport; glutamatergic neurotransmission; brain nerve terminals

1. Abbott N. J. Inflammatory mediators and modulation of blood-brain barrier permeability.  Cell. Mol. Neurobiol.  20, 131—147 (2000).

2. Borisova T., Himmelreich N. Centrifuge-Induced Hypergravity: [3H]GABA and L-[14C]glutamate Uptake, Exocytosis and Efflux Mediated by High-Affinity, Sodium-Dependent Transporters.  Adv. Space Res.  36, 1340—1345 (2005).  

3. Borisova T., Kasatkina L., Ostapchenko L. The proton gradient of secretory granules and glutamate transport in blood platelets during cholesterol depletion of the plasma membrane by methyl-beta-cyclodextrin.  Neurochem. Int.  59, 965—975 (2011).

4.  Borisova T., Krisanova N. Presynaptic transporter-mediated release of glutamate evoked by the protonophore FCCP increases under altered gravity conditions.  Adv. Space Res42, 1971—1979 (2008).  

5. Borisova T., Krisanova N., Himmelreich N. Exposure of animals to artificial gravity conditions leads to the alteration of the glutamate release from rat cerebral hemispheres nerve terminals.  Adv. Space Res.  33, 1362—1367 (2004). 

6. Borisova T., Krisanova N., Sivko R., Borysov A. Cholesterol depletion attenuates tonic release but increases the ambient level of glutamate in rat brain synaptosomes.  Neurochem. Int.  56, 466—478 (2010).

7. Borisova T., Krisanova N., Sivko R., et al. Presynaptic malfunction: The neurotoxic effects of cadmium and lead on the proton gradient of synaptic vesicles and glutamate transport.  Neurochem. Int59, 272—279 (2011).

8. Borisova T., Sivko R., Borysov A., Krisanova N. Diverse presynaptic mechanisms underlying methyl-beta-cyclo-dextrin-mediated changes in glutamate transport.  Cell. Mol. Neurobiol.  30, 1013—1023 (2010).

9. Bourdon J. A., Saber A. T., Jacobsen N. R., et al. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver.  Part. Fibre. Toxicol. 9-5 (2012).

10. Chatterjee A., Wang A., Lera M., Bhattacharya S. Lunar soil simulant uptake produces a concentration-dependent increase in inducible nitric oxide synthase expression in murine RAW 264.7 macrophage cells.  J. Toxicol. Environ. Health A.  73, 623—636 (2010).

11. Choi S. J., Oh J. M., Choy J. H. Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells.  J. Inorg. Biochem.  103, 463—471 (2009).

12. Cotman C. W. Isolation of synaptosomal and synaptic plasma membrane fractions.  Meth. Enzymol.  31, 445—452 (1974).

13. Danbolt N. C. Glutamate uptake.  Prog. Neurobiol.  65, 1—105 (2001).

14. Darquenne C., Prisk G. Deposition of inhaled particles in the human lung is more peripheral in lunar than in normal gravity.  Eur. J. Appl. Physiol.  103, 687— 695 (2008).

15. Frampton M. W., Stewart J. C., Oberdorster G., et al. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans.  Environ. Health Perspect. 114, 51—58 (2006).  

16. Fubini B., Fenoglio I. Toxic potential of mineral dusts.  Elements.  3, 407—414 (2007).

17. Garred I., Rodal S. K., van Deurs B., Sandvig K. Reconstitution of clathrin-independent endocytosis at the apical domain of permeabilized MDCK II cells: requirement for a Rho-family GTPase.  Traffic.  2, 26—36 (2001).

18. Geiser M., Rothen-Rutishauser B., Kapp N., et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.  Environ. Health. Perspect.  113, 1555—1560 (2005).

19. Halatek T., Sinczuk-Walczak H., Rydzynski K. Early neurotoxic effects of inhalation exposure to aluminum and/ or manganese assessed by serum levels of phospholipidbinding Clara cells protein.  J. Environ. Sci. Health. A Tox. Hazard. Subst. Environ. Eng.  43, 118—124 (2008).

20. Kao Y. Y., Cheng T. J., Yang D. M. Demonstration of an olfactory Bulb—Brain translocation pathway for ZnO nanoparticles in rodent cells in vitro and in vivo.  J. Mol. Neurosci.  48, 464—471 (2012).

21. Kasatkina L., Borisova T. Impaired Na+-dependent glutamate uptake in platelets during depolarization of their plasma membrane.  Neurochem. Int.  56, 711—719 (2010).

22. Krisanova N., Sivko R., Kasatkina L., Borisova T. Neuroprotection by lowering cholesterol: A decrease in membrane cholesterol content reduces transporter-mediated glutamate release from brain nerve terminals.  Biochim. Biophys. Acta. Mol. Bas. Dis.  1822 (10), 1553—1561 (2012).

23. Krisanova N., Trikash I., Borisova T. Synaptopathy under conditions of altered gravity: Changes in synaptic vesicle fusion and glutamate release.  Neurochem. Int.  55, 724—731 (2009).

24. Lam C. W, James J. T, Latch J. N, et al. Pulmonary toxicity of simulated lunar and Martian dusts in mice: II. Biomarkers of acute responses after intratracheal instillation.  Inhal. Toxicol.  14, 917—928 (2002).

25. Lam C. W., James J. T., McCluskey R., et al. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation.  Inhal. Toxicol14, 901—916 (2002).

26. Larson E., Howlett B., Jagendorf A. Artificial reductant enhancement of the Lowry method for protein determination.  Anal. Biochem. 155, 243—248 (1986).

27. Latch J. N., Hamilton R. F. Jr., Holian A., et al. Toxicity of lunar and martian dust simulants to alveolar macrophages isolated from human volunteers.  Inhal. Toxicol.  20, 157—165 (2008).

28. Linnarsson D., Carpenter J., Fubini B., et al. Toxicity of lunardust.  Planet. and Space Sci. 10.1016/ j.pss.2012.05. 023 (2012).

29. Loftus D. J., Rask J. C., McCrossin C. G., Tranfield E. M. The chemical reactivity of lunar dust: from toxicity to astrobiology physics and astronomy.  Earth, Moon, and Planets.  107, 95—105 (2010).

30. Mikawa M., Kato H., Okumura M., et al. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents.  Bioconjug. Chem12, 510—514 (2001).

31. Morimoto Y., Miki T., Higashi T., et al. [Effect of lunar dust on humans: -lunar dust: regolith-].  Nihon Eiseigaku Zasshi.  65, 479—485 (2010).

32. Oberdorster G., Sharp Z., Atudorei V., et al. Translocation of inhaled ultrafine particles to the brain.  Inhal. Toxicol.  16, 437—445 (2004).

33. Peterson J. B., Prisk G. K., Darquenne C. Aerosol deposition in the human lung periphery is increased by reduced-density gas breathing.  J. Aerosol. Med. Pulm. Drug Del.  21, 159—168 (2008).

34. Qingnuan L., Yan X., Xiaodong Z., et al. Preparation of (99m)Tc-C(60)(OH)(x) and its biodistribution studies.  Nucl. Med. Biol.  29, 707—710 (2002).

35. Rehders M., Grosshluser B. B., Smarandache A., et al. Effects of lunar and mars dust simulants on HaCaT keratinocytes and CHO-K1 fibroblasts.  Adv. Space Res.  47, 1200—1213 (2011).

36. Takeda K., Suzuki K. I., Ishihara A., et al. Nanoparticles transferred from pregnant mice to their offspring can damage the genital and cranial nerve systems.  J. Health. Sci. 55, 95—102 (2009).

37. Tarasenko A. S., Sivko R. V., Krisanova N. V., et al. Cholesterol depletion from the plasma membrane impairs proton and glutamate storage in synaptic vesicles of nerve terminals.  J. Mol. Neurosci.  41, 358—367 (2010).

38. Wallace W. T., Tayler L. A., Liu Y., et al. Lunar dust and lunar simulant activation and monitoring.  Meteorit. Planet. Sci.  44, 961—970 (2009).

39. Wang H., Wang J., Deng X., et al. Biodistribution of carbon single-wall carbon nanotubes in mice.  J. Nanosci. Nanotech.  4, 1019—1024 (2004).

40. Xia T., Kovochich M., Liong M., et al. Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways.  ACS Nano2, 85—96 (2008).