title: Neurotoxic potential of lunar and martian dust: influence on em, proton gradient, active transport, and binding of glutamate in rat brain nerve terminals.
abstract: The harmful effects of lunar dust (LD) on directly exposed tissues are documented in the literature, whereas researchers are only recently beginning to consider its effects on indirectly exposed tissues. During inhalation, nano-/microsized particles are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of LD and martian dust (MD) has not yet been assessed. Glutamate is the main excitatory neurotransmitter involved in most aspects of normal brain function, whereas disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The research was focused on the analysis of the effects of LD/MD simulants (JSC-1a/JSC, derived from volcanic ash) on the key characteristics of glutamatergic neurotransmission. The average size of LD and MD particles (even minor fractions) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled l-[(14)C]glutamate, it was shown that there is an increase in l-[(14)C]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Na(+)] media and at low temperature in the presence of LD. MD caused significantly lesser changes under the same conditions, whereas nanoparticles of magnetite had no effect at all. Fluorimetric experiments with potential-sensitive dye rhodamine 6G and pH-sensitive dye acridine orange showed that the potential of the plasma membrane of the nerve terminals and acidification of synaptic vesicles were not altered by LD/MD (and nanoparticles of magnetite). Thus, the unique effect of LD to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on extracellular glutamate homeostasis in the central nervous system and cause alterations in the ambient level of glutamate, which 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.
authors.affiliation: Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Krisanova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kasatkina
authors.forename: Roman
authors.initials: R
authors.lastname: Sivko
authors.forename: Arseniy
authors.initials: A
authors.lastname: Borysov
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Nazarova
authors.forename: Klaus
authors.initials: K
authors.lastname: Slenzka
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borisova
mesh_terms: D000165:Acridine Orange; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D004391:Dust; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018535:Mars; D008564:Membrane Potentials / Q000187:drug effects; D016081:Moon; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines; D013569:Synapses / Q000187:drug effects*; D018675:Toxicity Tests
chemical_list: D002250:Carbon Radioisotopes; D004391:Dust; D005456:Fluorescent Dyes; D009498:Neurotoxins; D012235:Rhodamines; C026188:rhodamine 6G; D018698:Glutamic Acid; D000165:Acridine Orange
references.citation: Cell Mol Neurobiol. 2010 Oct;30(7):1013-23
references.pmid: 20502957
references.citation: Adv Space Res. 2004;33(8):1362-7
references.pmid: 15803628
references.citation: Bioconjug Chem. 2001 Jul-Aug;12(4):510-4
references.pmid: 11459454
references.citation: Neurochem Int. 2010 Apr;56(5):711-9
references.pmid: 20170696
references.citation: Inhal Toxicol. 2008 Jan;20(2):157-65
references.pmid: 18236230
references.citation: J Mol Neurosci. 2012 Oct;48(2):464-71
references.pmid: 22528453
references.citation: Environ Health Perspect. 2005 Nov;113(11):1555-60
references.pmid: 16263511
references.citation: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2008 Feb;43(2):118-24
references.pmid: 18172803
references.citation: Prog Neurobiol. 2001 Sep;65(1):1-105
references.pmid: 11369436
references.citation: Neurochem Int. 2011 Aug;59(2):272-9
references.pmid: 21672571
references.citation: Eur J Appl Physiol. 2008 Aug;103(6):687-95
references.pmid: 18488244
references.citation: ACS Nano. 2008 Jan;2(1):85-96
references.pmid: 19206551
references.citation: Biochim Biophys Acta. 2012 Oct;1822(10):1553-61
references.pmid: 22713486
references.citation: Acc Chem Res. 2013 Mar 19;46(3):714-22
references.pmid: 22980029
references.citation: Part Fibre Toxicol. 2012 Feb 02;9:5
references.pmid: 22300514
references.citation: J Aerosol Med Pulm Drug Deliv. 2008 Jun;21(2):159-68
references.pmid: 18518792
references.citation: Cell Mol Neurobiol. 2000 Apr;20(2):131-47
references.pmid: 10696506
references.citation: Environ Health Perspect. 1994 Oct;102 Suppl 5:173-9
references.pmid: 7882925
references.citation: Nihon Eiseigaku Zasshi. 2010 Sep;65(4):479-85
references.pmid: 20885072
references.citation: Methods Enzymol. 1974;31:445-52
references.pmid: 4278474
references.citation: J Mol Neurosci. 2010 Jul;41(3):358-67
references.pmid: 20369388
references.citation: Traffic. 2001 Jan;2(1):26-36
references.pmid: 11208166
references.citation: Nucl Med Biol. 2002 Aug;29(6):707-10
references.pmid: 12234597
references.citation: Inhal Toxicol. 1996;8 Suppl:73-89
references.pmid: 11542496
references.citation: Neurochem Int. 2011 Nov;59(6):965-75
references.pmid: 21787821
references.citation: J Inorg Biochem. 2009 Mar;103(3):463-71
references.pmid: 19181388
references.citation: Anal Biochem. 1986 Jun;155(2):243-8
references.pmid: 3728976
references.citation: J Toxicol Environ Health A. 2002 Oct 25;65(20):1531-43
references.pmid: 12396867
references.citation: J Toxicol Environ Health A. 2010;73(9):623-6
references.pmid: 20391141
references.citation: Neurochem Int. 2010 Feb;56(3):466-78
references.pmid: 20025918
references.citation: Inhal Toxicol. 2002 Sep;14(9):901-16
references.pmid: 12396402
references.citation: J Nanosci Nanotechnol. 2004 Nov;4(8):1019-24
references.pmid: 15656196
references.citation: Neurochem Int. 2009 Dec;55(8):724-31
references.pmid: 19631248
references.citation: Inhal Toxicol. 2004 Jun;16(6-7):437-45
references.pmid: 15204759
references.citation: Inhal Toxicol. 2002 Sep;14(9):917-28
references.pmid: 12396403
references.citation: Environ Health Perspect. 2006 Jan;114(1):51-8
references.pmid: 16393658