Aim. In biomedical applications, silica nanoparticles are promising for controlled drug delivery. Also, from an environmental point of view, silica accounts for the most significant part of the mass of air pollution, particularly matter components, especially during sand dust storms. Methods. Amino-grafted mesoporous silica nanoparticles (MSN-NH2) were synthesized by means of co-condensation of tetraethoxysilane and 3-aminopropyltriethoxysilane and characterized using TEM, IR-spectroscopy, and powder X-ray diffraction. Neuromodulatory and related properties of MSN-NH2 were evaluated using rat cortex nerve terminals (synaptosomes). Results. MSN-NH2 did not influence the extracellular synaptosomal level of excitatory neurotransmitter L-[14C]glutamate and so did not cause excitotoxicity. In fluorescence measurements, MSN-NH2 depolarised the synaptosomal membrane and demonstrated weak antioxidant properties, decreasing the spontaneous generation of reactive oxygen species, whereas MSN-NH2 did not alter H2O2 in nerve terminals. The model of Cd2+/Pb2+/Hg2+-induced excitotoxicity was used to assess the capability of MSN-NH2 to adsorb xenobiotic heavy metals. MSN-NH2 did not modulate the Cd2+/Pb2+/Hg2+-induced increase in the extracellular synaptosomal level of L-[14C]glutamate. Conclusion. MSN-NH2 did not demonstrate excitotoxic signs, had weak antioxidant properties, and was biocompatible. MSN-NH2 did not mitigate the excitotoxic effects of xenobiotic heavy metals and did not adsorb these metals in biological systems.

Aim. Carbon particles have been widely used in different technologies and have great potential for new biological application. Synthesis of carbon particles from agricultural waste using “green” principles is in the mainstream of biotechnology area and attract a great attention in biomedical application. Here, coarse carbon particles (CCPs) were synthesized using “green” principles from dry apple and used in the biological experiments without preliminary functionalization. Methods. Neurotoxic features of CCPs were analysed in isolated presynaptic cortex nerve terminals (synaptosomes) monitoring the extracellular levels of excitatory neurotransmitter L-[14C] glutamate and inhibitory one [3H]GABA, as well as the membrane potential. Results. Measuring the membrane potential of the nerve terminals, it was revealed an inadequate decrease in the fluorescence intensity of the potential-dependent dye rhodamine 6G in the presence of CCPs (1 mg/ml). This decrease was not due to membrane hyperpolarisation because CCPs did not change the extracellular synaptosomal levels of L-[14C] glutamate and [3H]GABA. CCP-induced decrease in the fluorescence intensity of the dye in nerve terminals can be due to its interaction with CCPs. Indeed, the ability of CCPs to interact with rhodamine 6G was shown in synaptosome-free incubation media. Conclusions. Therefore, CCPs did not possess neurotoxic signs, and so are biocompatible. In both experiments, i.e. without bio object and in biological system, CCPs were able to interact with fluorescent dye rhodamine 6G. In prospect, this feature of CCPs can be used in biotechnology after further investigation of dye interaction conditions.

A study of the infrared spectrum of the environment of the planetary nebula Tc 1 revealed the radiation of cold and neutral fullerenes C60 and C70. The results of the analysis of infrared spectra obtained using the Hubble space telescope conclusively proved the existence of C60+ fullerene in the interstellar medium. These large carbon-containing molecules can form and exist in the interstellar medium and are candidates to explain many diffuse interstellar absorption bands. In this study, the potential neuroactivity of the C60 fullerene as a planetary dust component was assessed in the isolated rat brain nerve terminals. It was shown that C60 fullerene in the unirradiated state at concentrations of 0.05-0.25 mg/ml did not change the extracellular levels of excitatory neurotransmitter L-[14C]glutamate and inhibitory neurotransmitter [3H]GABA in the preparations of rat brain nerve terminals. An increase in fullerene C60 concentrations up to 0.5 and 1.00 mg/ml was accompanied by an increase in the extracellular levels of L-[14C]glutamate and [3H]GABA in the preparations of nerve terminals. Therefore, fullerene C60 did not cause signs of acute neurotoxicity in the brain nerve terminals within the concentration range of 0.05-0.25 mg/ml. However, given that C60 undergoes photooxidation, it can be expected that it may acquire neurotoxic properties in situ.

Levetiracetam (LV), 2S-(2-oxo-1-pyrrolidiny1) butanamide, is an antiepileptic drug. The exact mechanisms of anticonvulsant effects of LV remain unclear. In this study, rats (Wistar strain) underwent hypoxia and seizures at the age of 10–12 postnatal days (pd). [3H]GABA release was analysed in isolated from thalamus nerve terminals (synaptosomes) during development at the age of pd 17–19 and pd 24–26 (infantile stage), pd 38–40 (puberty) and pd 66–73 (young adults) in control and after perinatal hypoxia. The extracellular level of [3H]GABA in the preparation of thalamic synaptosomes increased during development at the age of pd 38–40 and pd 66–73 as compared to earlier ones. LV did not influence the extracellular level of [3H]GABA in control and after perinatal hypoxia at all studied ages. Exocytotic [3H]GABA release in control increased at the age of pd 24–26 as compared to pd 17–19. After hypoxia, exocytotic [3H]GABA release from synaptosomes also increased during development. LV elevated [3H]GABA release from thalamic synaptosomes at the age of pd 66–73 after hypoxia and during blockage of GABA uptake by NO-711 only. LV realizes its antiepileptic effects at the presynaptic site through an increase in exocytotic release of [3H]GABA in thalamic synaptosomes after perinatal hypoxia at pd 66–73. LV exhibited a more significant effect in thalamic synaptosomes after perinatal hypoxia than in control ones. The action of LV is age-dependent, and the drug was inert at the infantile stage that can be useful for an LV application strategy in child epilepsy therapy. Keywords: brain development, exocytosis, GABA, levetiracetam, perinatal hypoxia, thalamic synaptosomes

Nowadays, analysis of the mechanisms of brain malfunctioning under conditions of long-term manned space missions is a priority research area of international scientific groups and an urgent task of modern space biology. Ignoring the problems of the nervous system functioning can make impossible further long-term interplanetary space missions. One of the possible causes of brain impairment can be an exposure to planetary and interstellar dust, whose composition, properties, and the impact on human health, in particular, neurotoxicity, have not been sufficiently investigated. Carbon is widely distributed in the native Martian dust and interstellar space and is a part of meteorites. In this study, the inorganic analog of Martian dust (MD) (JSC, Mars-1A, ORBITEC Orbital Technologies Corporation, Madison, Wisconsin, USA) was enriched in different amounts by carbon nanoparticles (CNP) synthesized by the combustion of carbohydrates. MD enriched with CNP (CNP-MD) depolarizes the plasma membrane of the rat brain nerve terminals as shown by fluorimetry using a rhodamine 6G fluorescent probe. An increase in the content of the carbon component of the CNP-MD is accompanied by an increase in the depolarization of the membrane. CNP-MD significantly reduces the initial rate of accumulation and increases the extracellular level of the neurotransmitters L-[C-14] glutamate and [H-3]GABA (gamma-aminobutyric acid) in the nerve terminals. An increase of CNP content in CNP-MD is accompanied by a more significant decrease in the initial rate of neurotransmitter uptake and an increase in their extracellular level. Therefore, the neurotoxic effect of CNP-MD is associated exclusively with the CNP activity but not with the action of its inorganic component. A decrease in the CNP content in CNP-MD reduces its neurotoxicity.

The manned extraterrestrial missions and planetary exploration require an assessment of the toxicity of planetary dust. Preparation of perspective space missions (especially Lunar station-related upcoming plans) requires urgent development of a methodology for the rapid assessment of toxicity of environmental compounds. Recently, the working group of the project was the first who showed the absence of significant neurotoxic effects of Lunar and Martian dust simulants, but the toxic properties of a mixture of Martian dust simulant particles and carbon nanoparticles. These experimental data were published in peer-reviewed journals, such as Microgravity Science and Technology (Pozdnyakova et al., 2017) and in the special issue of American Institute of Aeronautics and Astronautics (Dunne et al., 2010). The proposed project involves the development of a new methodology, evaluation algorithm, and equipment, as well as relevant models that can predict and determine the biosecurity of dust particles.

Carbon is widely distributed in the Martian dust, meteorites and interstellar space. In this study, we prepared carbon-containing Martian dust analogue, which consists of inorganic Martian dust simulant derived from volcanic ash (JSC, Mars1A, ORBITEC, USA) and carbon (nanodiamonds). The aim of the study was to analyze the effects of carbon-containing Martian dust analogue on the key characteristics of the synaptic neurotransmission. It was shown that the carbon-containing Martian dust analogue enriched with nanodiamonds significantly reduced the initial rate of accumulation and increased extracellular levels of neurotransmitters L-[C-14] glutamate and [H-3] GABA (gamma-aminobutyric acid) in isolated rat brain nerve terminals. These effects of carbon-containing Martian dust analogue were mainly associated to the activity of its carbon component, but not to inorganic components. So, carbon component of native Martian dust can have deleterious effects on extracellular glutamate and GABA homeostasis in the CNS, and so glutamate-and GABA-ergic neurtransmission, disballansing exitatory and inhibitory signals. Thus, the toxic effects of carbon structures in native Martian dust, soil, and meteorites for human health may be greater than the effect of the inorganic components.

The effects of highly-selective blocker of γ-aminobutyric acid transporters of GAT1, NO-711, and substrate inhibitor of γ aminobutyric acid transporters GAT3, ß-alanine on the initial velocity of L-[14C]glutamate and [3H]-γ-aminobutyric acid uptake by cortical, hippocampal and thalamic nerve terminals (synaptosomes) were analyzed in norm and after perinatal hypoxia. Rats were underwent to hypoxia and seizures (airtight chamber, 4% O2 and 96% N2) at the age of 10–12 postnatal days. The experiments were performed at 8–9 weeks in the control and after hypoxia. It was shown that NO-711 (30 microM) and ß-alanine (100 microM) did not affect initial velocity of L-[14C] glutamate uptake by cortical, hippocampal and thalamic synaptosomes. In cortical synaptosomes, NO-711 and ß-alanine decreased the initial velocity of [3H]-γ-aminobutyric acid uptake, but their inhibitory effects were similar in control and hypoxia groups. The effectiveness of ß-alanine to influence [3H]-γ-aminobutyric acid uptake was increased in hippocampal and thalamic nerve terminals as a result of perinatal hypoxia, whereas the capacity of NO-711 in thalamic nerve terminals was decreased. These results suggest changes in the ratio of active GAT1/GAT3 expressed in the plasma membrane of nerve terminals after perinatal hypoxia. Thus, ß-alanine is a promising substance for development of neurotropic pharmacological preparations for the transporter-mediated regulation of GABA-ergic neurotransmission.