Substitution of bridge carbons for sulphur in calix[4]arene-bis-α-hydroxymethylphosphonic acid transformed mobile carrier into ionic channel accompanied with evoked muscle contraction and impaired neurotransmission powered by membrane action of resulting thiocalix[4]arene-bis-α-hydroxymethylphosphonic acid.

The action of calix[4]arenes C-424, C-425 and C-1193 has been investigated on suspended cholesterol/egg phosphatidylcholine lipid bilayer in a voltage-clamp mode. Comparative analysis with the membrane action by calix[4]arene-bis-α-hydroxymethylphosphonic acid (C-99) has shown that the substitution of bridge carbons for sulphur and addition of another methyl group to two alkyl tales in the lower rim of former dipropoxycalix[4]arene C-99 transformed mobile carrier that C-99 created in lipid bilayer (Shatursky et al., 2014) into a transmembrane pore as exposure of the bilayer membrane to sulphur-containing derivative dibutoxythiocalix[4]arene C-1193 resulted in microscopic transmembrane current patterns indicative of a channel-like mode of facilitated diffusion. Within all calix[4]arenes tested a net steady-state voltage-dependent transmembrane current was readily achieved only after addition of calix[4]-arene C-1193. In comparison with the membrane action of C-99 the current induced by calix[4]-arene C-1193 exhibited a much weakened anion selectivity passing slightly more current at positive potentials applied from the side of bilayer membrane to which the calix[4]-arene was added. Testing C-1193 for the membrane action against smooth muscle cells of rat uterus or swine myometrium and synaptosomes of rat brain nerve terminals revealed an increase in intracellular concentration of Ca2+ with reduction of the effective hydrodynamic diameter of the smooth muscle cells and enhanced basal extracellular level of neurotransmitters (glutamate and γ-aminobutyric acid) after C-1193-induced depolarization of the nerve terminals.

Multipollutant reciprocal neurological hazard from smoke particulate matter and heavy metals cadmium and lead in brain nerve terminals.

Heavy metals, Cd2+ and Pb2+, and carbonaceous air pollution particulate matter are hazardous neurotoxicants. Here, a capability of water-suspended smoke particulate matter preparations obtained from poplar wood (WPs) and polypropylene fibers (medical facemasks) (MPs) to influence Cd2+/Pb2+-induced neurotoxicity, and vice versa, was monitored using biological system, i.e. isolated presynaptic rat cortex nerve terminals. Combined application of Pb2+ and WPs/MPs to nerve terminals in an acute manner revealed that smoke preparations did not change a Pb2+-induced increase in the extracellular levels of excitatory neurotransmitter L-[14C]glutamate and inhibitory one [3H]GABA, thereby demonstrating additive result and no interference of neurotoxic effects of Pb2+ and particulate matter. Whereas, both smoke preparations decreased a Cd2+-induced increase in the extracellular level of L-[14C]glutamate and [3H]GABA in nerve terminals. In fluorimetric measurements, the metals and smoke preparations demonstrated additive effects on the membrane potential of nerve terminals causing membrane depolarisation. WPs/MPs-induced reduction of spontaneous ROS generation was mitigated by Cd2+ and Pb2+. Therefore, a potential variety of multipollutant heavy metal-/airborne particulate-induced effects on key presynaptic processes was revealed. Multipollutant reciprocal neurological hazard through disturbance of the excitation-inhibition balance, membrane potential and ROS generation was evidenced. This multipollutant approach and data contribute to up-to-date environmental quality/health risk estimation.

Mercury-induced excitotoxicity in presynaptic brain nerve terminals: modulatory effects of carbonaceous airborne particulate simulants.

Multipollutant approach is a breakthrough in up-to-date environmental quality and health risk estimation. Both mercury and carbonaceous air particulate are hazardous neurotoxicants. Here, the ability of carbonaceous air particulate simulants, i.e. carbon dots obtained by heating of organics, and nanodiamonds, to influence Hg2+-induced neurotoxicity was monitored using biological system, i.e. presynaptic rat cortex nerve terminals. Using HgCl2 and classical reducing/chelating agents, an adequate synaptic parameter, i.e. the extracellular level of key excitatory neurotransmitter L-[14C]glutamate, was selected for further analysis. HgCl2 starting from 5 µM caused an acute and concentration-dependent increase in the extracellular L-[14C]glutamate level in nerve terminals. Combined application of Hg2+ and carbon dots from heating of citric acid/urea showed that this simulant was able to mitigate in an acute manner excitotoxic Hg2+-induced increase in the extracellular L-[14C]glutamate level in nerve terminals by 37%. These carbon dots and Hg2+ acted as a complex in nerve terminals that was confirmed with fluorimetric data on Hg2+-induced changes in their spectroscopic features. Nanodiamonds and carbon dots from ß-alanine were not able to mitigate a Hg2+-induced increase in the extracellular L-[14C]glutamate level in nerve terminals. Developed approach can be applicable for monitoring capability of different particles/compounds to have Hg2+-chelating signs in the biological systems. Therefore, among testing simulants, the only carbon dots from citric acid/urea were able to mitigate acute Hg2+-induced neurotoxicity in nerve terminals, thereby showing a variety of effects of carbonaceous airborne particulate in situ and its potential to interfere and modulate Hg2+-associated health hazard.

Disposable facemask waste combustion emits neuroactive smoke particulate matter.

Tremendous deposits of disposable medical facemask waste after the COVID-19 pandemic require improvement of waste management practice according to WHO report 2022, moreover facemasks are still in use around the world to protect against numerous airborne infections. Here, water-suspended smoke preparations from the combustion of disposable medical facemasks (polypropylene fibers) were collected; size, zeta potential, surface groups of smoke particulate matter were determined by dynamic light scattering, FTIR and Raman spectroscopy, and their optical properties were characterized. Neurochemical study using nerve terminals isolated from rat cortex revealed a significant decrease in the initial rate of the uptake/accumulation of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H]GABA, and exocytotic release, and also an increase in the extracellular level of these neurotransmitters. Fluorescent measurements revealed that ROS generation induced by hydrogen peroxide and glutamate receptor agonist kainate decreased in nerve terminals. A decrease in the membrane potential of nerve terminals and isolated neurons, the mitochondrial potential and synaptic vesicle acidification was also shown. Therefore, accidental or intentional utilization of disposable medical facemask waste by combustion results in the release of neuroactive ultrafine particulate matter to the environment, thereby contributing to plastic-associated pollution of air and water resources and neuropathology development and expansion.

Rhizobacteria Increase the Adaptation Potential of Potato Microclones under Aeroponic Conditions.

Adaptation ex vitro is strongly stressful for microplants. Plant-growth-promoting rhizobacteria (PGPR) help to increase the adaptation potential of microplants transplanted from test tubes into the natural environment. We investigated the mechanisms of antioxidant protection of PGPR-inoculated potato microclones adapting to ex vitro growth in an aeroponic system. Potato (Solanum tuberosum L. cv. Nevsky) microplants were inoculated in vitro with the bacteria Azospirillum baldaniorum Sp245 and Ochrobactrum cytisi IPA7.2. On days 1 and 7 of plant growth ex vitro, catalase and peroxidase activities in the leaves of inoculated plants were 1.5-fold higher than they were in non-inoculated plants. The activity of ascorbate peroxidase was reduced in both in vitro and ex vitro treatments, and this reduction was accompanied by a decrease in the leaf content of hydrogen peroxide and malondialdehyde. As a result, inoculation contributed to the regulation of the plant pro/antioxidant system, lowering the oxidative stress and leading to better plant survival ex vitro. This was evidenced by the higher values of measured morphological and physiological variables of the inoculated plants, as compared with the values in the control treatment. Thus, we have shown some PGPR-mediated mechanisms of potato plant protection from adverse environmental factors under aeroponic conditions.

A comparative multi-level toxicity assessment of carbon-based Gd-free dots and Gd-doped nanohybrids from coffee waste: hematology, biochemistry, histopathology and neurobiology study.

Here, a comparative toxicity assessment of precursor carbon dots from coffee waste (cofCDs) obtained using green chemistry principles and Gd-doped nanohybrids (cofNHs) was performed using hematological, biochemical, histopathological assays in vivo (CD1 mice, intraperitoneal administration, 14 days), and neurochemical approach in vitro (rat cortex nerve terminals, synaptosomes). Serum biochemistry data revealed similar changes in cofCDs and cofNHs-treated groups, i.e. no changes in liver enzymes' activities and creatinine, but decreased urea and total protein values. Hematology data demonstrated increased lymphocytes and concomitantly decreased granulocytes in both groups, which could evidence inflammatory processes in the organism and was confirmed by liver histopathology; decreased red blood cell-associated parameters and platelet count, and increased mean platelet volume, which might indicate concerns with platelet maturation and was confirmed by spleen histopathology. So, relative safety of both cofCDs and cofNHs for kidney, liver and spleen was shown, whereas there were concerns about platelet maturation and erythropoiesis. In acute neurotoxicity study, cofCDs and cofNHs (0.01 mg/ml) did not affect the extracellular level of L-[14C]glutamate and [3H]GABA in nerve terminal preparations. Therefore, cofNHs demonstrated minimal changes in serum biochemistry and hematology assays, had no acute neurotoxicity signs, and can be considered as perspective biocompatible non-toxic theragnostic agent.

Degradation of a Model Mixture of PAHs by Bacterial-Fungal Co-Cultures.

BACKGROUND: Bacteria and fungi are the most important soil organisms owing to their abundance and the key roles they play in the functioning of ecosystems. We examined possible synergistic and antagonistic effects during the degradation of polycyclic aromatic hydrocarbons (PAHs) by co-cultures of ascomycetes and a plant-growth-promoting bacterium. METHODS: Bacteria and fungi were grown in a liquid nutrient medium supplemented with PAHs. The PAH degradations and the identification of metabolites were checked by high-performance liquid chromatography (HPLC). Enzymatic activities were measured spectrophotometrically using test substrates. All experimental treatments were analyzed using Excel 2019 (Microsoft Office 2019, USA). RESULTS: The model system included the plant-growth-promoting rhizobacterium (PGPR) Azospirillum brasilense and one of the following ascomycetes: Fusarium oxysporum (plant pathogen), Talaromyces sayulitensis (rhizospheric fungus), Trichoderma viride (plant-growth-promoting fungus, PGPF), and Trichoderma harzianum (PGPF). The notable results are: (1) synergistic effects consisted of more active utilization of the PAH mixture compared to individual compounds, while the PAH mixture was more actively degraded by co-cultures than monocultures; (2) three effects of mutual influence by the studied organisms were also revealed: depressing (F. oxysporum and A. brasilense), partially depressing (T. sayulitensis suppressed the growth of A. brasilense but increased the degradation of anthracene, pyrene, and fluoranthene), and positive effects (A. brasilense and T. viride or T. harzianum); (3) for the first time quinone metabolites of PAH degradation and extracellular oxidase and peroxidase were produced during PAH degradation by T. sayulitensis.Conclusions: The results of the study contribute to the understanding of bacterial-fungal interactions in polluted settings.

Similar in vitro response of rat brain nerve terminals, colon preparations and COLO 205 cells to smoke particulate matter from different types of wood.

Major source of carbon-containing air born particular matter that significantly pollutes environment and provokes development of neuropathology is forest fires and wood combustion. Here, water-suspended smoke particulate matter preparations (SPs) were synthesized from birch, pine, poplar wood, and also birch bark and pine needles. Taking into account importance of the gut-brain communication system, SP properties were compared regarding their capability to modulate functioning of nerve terminals and gut cells/preparations. In cortex nerve terminals, poplar wood SP was more effective in decreasing uptake and increasing the extracellular levels of excitatory and inhibitory neurotransmitters L-[14C]glutamate and [3H]GABA, respectively. Spontaneous and H2O2-stimulated ROS generation in nerve terminals decreased by SPs, the most efficient one was from poplar wood. SPs from birch, pine and poplar wood caused membrane depolarization, poplar wood SP effect was 5-fold higher vs. birch and pine wood ones. Functional characteristics of gut cells/preparations, which tightly related to nerve terminal experiments, were assessed. SPs increased paracellular permeability of proximal colon mucosal-submucosal preparations monitored in Ussing chamber system (FITC-dextran, 4 kDa), where the most prominent effect had poplar wood SP. The latter demonstrated more considerable influence on COLO 205 cell causing 30 % loss of cell viability. PM emitted to the environment during combustion of various wood caused similar unidirectional harmful effects on brain and gut cell functioning, thereby triggering development of pathologies in gut and brain and gut-brain communication system.

Neuromodulation by selective angiotensin-converting enzyme 2 inhibitors.

Here, neuromodulatory effects of selective angiotensin-converting enzyme 2 (ACE2) inhibitors were investigated. Two different types of small molecule ligands for ACE2 inhibition were selected using chemical genetic approach, they were synthesized using developed chemical method and tested using presynaptic rat brain nerve terminals (synaptosomes). EBC-36032 (1 µM) increased in a dose-dependent manner spontaneous and stimulated ROS generation in nerve terminals that was of non-mitochondrial origin. Another inhibitor EBC-36033 (MLN-4760) was inert regarding modulation of ROS generation. EBC-36032 and EBC-36033 (100 µM) did not modulate the exocytotic release of L-[14C]glutamate, whereas both inhibitors decreased the initial rate of uptake, but not accumulation (10 min) of L-[14C]glutamate by nerve terminals. EBC-36032 (100 µM) decreased the exocytotic release as well as the initial rate and accumulation of [3H]GABA by nerve terminals. EBC-36032 and EBC-36033 did not change the extracellular levels and transporter-mediated release of [3H]GABA and L-[14C]glutamate, and tonic leakage of [3H]GABA from nerve terminals. Therefore, synthesized selective ACE2 inhibitors decreased uptake of glutamate and GABA as well as exocytosis of GABA at the presynaptic level. The initial rate of glutamate uptake was the only parameter that was mitigated by both ACE2 inhibitors despite stereochemistry issues. In terms of ACE2-targeted antiviral/anti-SARS-CoV-2 and other therapies, novel ACE2 inhibitors should be checked on the subject of possible renin-angiotensin system (RAS)-independent neurological side effects.

Effect of remediation techniques on petroleum removal from and on biological activity of a drought-stressed Kastanozem soil.

Many petroleum extraction and refinement plants are located in arid climates. Therefore, the remediation of petroleum-polluted soils is complicated by the low moisture conditions. We ran a 70-day experiment to test the efficacy of various combining of remediation treatments with sorghum, yellow medick, and biochar to remove petroleum from and change the biological activity of Kastanozem, a soil typical of the dry steppes and semideserts of the temperate zone. At normal moisture, the maximum petroleum-degradation rate (40%) was obtained with sorghum-biochar. At low moisture, the petroleum-degradation rate was 22 and 30% with yellow medick alone and with yellow medick - sorghum, respectively. Biochar and the biochar-plant interaction had little effect on soil remediation. Both plants promoted the numbers of soil microbes in their rhizosphere: yellow medick promoted mostly hydrocarbon-oxidizing microorganisms, whereas sorghum promoted both hydrocarbon-oxidizing and total heterotrophic microorganisms. Low moisture did not limit microbial development. In the rhizosphere of sorghum, dehydrogenase and urease activities were maximal at normal moisture, whereas in the rhizosphere of yellow medick, they were maximal at low moisture. Peroxidase activity was promoted by the plants in unpolluted soil and was close to the control values in polluted soil. Biochar and the biochar-plant interaction did not noticeably affect the biological activity of the soil.

Amphiphilic anti-SARS-CoV-2 drug remdesivir incorporates into the lipid bilayer and nerve terminal membranes influencing excitatory and inhibitory neurotransmission.

Remdesivir is a novel antiviral drug, which is active against the SARS-CoV-2 virus. Remdesivir is known to accumulate in the brain but it is not clear whether it influences the neurotransmission. Here we report diverse and pronounced effects of remdesivir on transportation and release of excitatory and inhibitory neurotransmitters in rat cortex nerve terminals (synaptosomes) in vitro. Direct incorporation of remdesivir molecules into the cellular membranes was shown by FTIR spectroscopy, planar phospholipid bilayer membranes and computational techniques. Remdesivir decreases depolarization-induced exocytotic release of L-[14C] glutamate and [3H] GABA, and also [3H] GABA uptake and extracellular level in synaptosomes in a dose-dependent manner. Fluorimetric studies confirmed remdesivir-induced impairment of exocytosis in nerve terminals and revealed a decrease in synaptic vesicle acidification. Our data suggest that remdesivir dosing during antiviral therapy should be precisely controlled to prevent possible neuromodulatory action at the presynaptic level. Further studies of neurotropic and membranotropic effects of remdesivir are necessary.

A comparative study of wood sawdust and plastic smoke particulate matter with a focus on spectroscopic, fluorescent, oxidative, and neuroactive properties.

Here, water-suspended smoke aerosol preparation was synthesized from biomass-based fuel, i.e., a widespread product for residential heating, wood sawdust (WP) (pine, poplar, and birch mixture), and its properties were compared in parallel experiments with the smoke preparation from plastics (PP). Molecular groups in the PM preparations were analyzed using Raman and Fourier-transform infrared spectroscopy. WP was assessed in neurotoxicity studies using rat cortex nerve terminals (synaptosomes). Generation of spontaneous and H2O2-evoked reactive oxygen species (ROS) detected using fluorescent dye 2',7'-dichlorofluorescein in nerve terminals was decreased by WP. In comparison with PP, WP demonstrated more pronounced reduction of spontaneous and H2O2-evoked ROS production. WP completely inhibited glutamate receptor agonist kainate-induced ROS production, thereby affecting the glutamate receptor-mediated signaling pathways. WP decreased the synaptosomal membrane potential in fluorimetric experiments and the synaptosomal transporter-mediated uptake of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H] γ-aminobutyric acid (GABA), respectively. PP decreased the ambient synaptosomal level of [3H]GABA, whereas it did not change that of L-[14C]glutamate. Principal difference between WP and PP was found in their ability to influence the ambient synaptosomal level of [3H]GABA (an increase and decrease, respectively), thereby showing riskiness in mitigation of synaptic inhibition by PP and triggering development of neuropathology.

The ability of carbon nanoparticles to increase transmembrane current of cations coincides with impaired synaptic neurotransmission.

Here, carbon nanodots synthesized from ß-alanine (Ala-CDs) and detonation nanodiamonds (NDs) were assessed using (1) radiolabeled excitatory neurotransmitters L-[14C]glutamate, D-[2,33H]aspartate, and inhibitory ones [3H]GABA, [3H]glycine for registration of their extracellular concentrations in rat cortex nerve terminals; (2) the fluorescent ratiometric probe NR12S and pH-sensitive probe acridine orange for registration of the membrane lipid order and synaptic vesicle acidification, respectively; (3) suspended bilayer lipid membrane (BLM) to monitor changes in transmembrane current. In nerve terminals, Ala-CDs and NDs increased the extracellular concentrations of neurotransmitters and decreased acidification of synaptic vesicles, whereas have not changed sufficiently the lipid order of membrane. Both nanoparticles, Ala-CDs and NDs, were capable of increasing the conductance of the BLM by inducing stable potential-dependent cation-selective pores. Introduction of divalent cations, Zn2+ or Cd2+ on the particles` application side (cis-side) increased the rate of Ala-CDs pore-formation in the BLM. The application of positive potential (+100 mV) to the cis-chamber with Ala-CDs or NDs also activated the insertion as compared with the negative potential (-100 mV). The Ala-CD pores exhibited a wide-range distribution of conductances between 10 and 60 pS and consecutive increase in conductance of each major peak by ~10 pS, which suggest the clustering of the same basic ion-conductive structure. NDs also formed ion-conductive pores ranging from 6 pS to 60 pS with the major peak of conductance at ~12 pS in cholesterol-containing membrane. Observed Ala-CDs and NDs-induced increase in transmembrane current coincides with disturbance of excitatory and inhibitory neurotransmitter transport in nerve terminals.

GABAA receptor agonist cinazepam and its active metabolite 3-hydroxyphenazepam act differently at the presynaptic site.

Cinazepam C19H14BrClN2O5, ("LevanaⓇ ІC") a partial GABAA receptor agonist, and its active metabolite 3-hydroxyphenazepam C15H10BrClN2O2 were comparatively assessed in vitro using nerve terminals isolated from rat cortex (synaptosomes). At the presynaptic site, cinazepam (100 and 200 µM) facilitated synaptosomal transporter-mediated [3H]GABA uptake by enhancing both the initial rate and accumulation, and decreased the ambient level and transporter-mediated release of [3H]GABA. Whereas, 3-hydroxyphenazepam decreased the uptake and did not change the ambient synaptosomal level and transporter-mediated release of [3H]GABA. To exclude GABA transporter influence, NO-711, the transporter blocker, was applied and it was found that exocytotic release of [3H]GABA decreased, whereas tonic release of [3H]GABA was not changed in the presence of both cinazepam or 3-hydroxyphenazepam after treatment of synaptosomes with NO-711. In fluorimetric studies using potential- and pH-sensitive dyes rhodamine 6G and acridine orange, respectively, it was found that cinazepam hyperpolarized the synaptosomal plasma membrane, and increased synaptic vesicle acidification, whereas, 3-hydroxyphenazepam demonstrated opposite effects on these parameters. Therefore, action of cinazepam and its active metabolite 3-hydroxyphenazepam on GABAergic neurotransmission was different. Therapeutic effects of cinazepam can be associated with its ability to hyperpolarize the plasma membrane, to increase synaptic vesicle acidification and capacity of its active metabolite 3-hydroxyphenazepam to inhibit GABA transporter functioning.

Unique features of brain metastases-targeted AGuIX nanoparticles vs their constituents: A focus on glutamate-/GABA-ergic neurotransmission in cortex nerve terminals.

Gadolinium-based radiosensitizing AGuIX nanoparticles (AGuIX) currently tested two phase 2 clinical trials in association with radiotherapy for the treatment of brain metastases. Here, excitatory/inhibitory neurotransmission was assessed in rat cortex nerve terminals in the presence of AGuIX and their constituents (DOTAGA and DOTAGA/Gd3+) at concentrations used for medical treatment, and those 5-24 times higher. The ambient level, transporter-mediated, tonic and exocytotic release of L-[14C]glutamate and [3H]GABA, the membrane potential of nerve terminals were not changed in the presence of AGuIX at concentrations used for medical treatment ([Gd3+] = 0.25 mM, corresponding to 0.25 g.L-1), and DOTAGA (0.25 mM) and DOTAGA/Gd3+ (0.25 mM/0.01 mM). Difference between AGuIX and the precursors was uncovered, when their concentrations were increased. AGuIX (1.25-6 mM) did not change any transport characteristics of L-[14C]glutamate and [3H]GABA, whereas, DOTAGA (1.25-6 mM) affected the membrane potential, ambient level, and exocytotic release of L-[14C]glutamate and [3H]GABA. Gd3+ did not mask, but even enhanced above effects of DOTAGA. Therefore, AGuIX did not influence glutamate- and GABA-ergic neurotransmission at the presynaptic site. In contrast, DOTAGA and mixture DOTAGA/Gd3+ significantly affected synaptic neurotransmission at high concentrations. AGuIX own structure that overcomes neurotoxic features of their constituents.

Inflammation/bioenergetics-associated neurodegenerative pathologies and concomitant diseases: a role of mitochondria targeted catalase and xanthophylls.

Various inflammatory stimuli are able to modify or even "re-program" the mitochondrial metabolism that results in generation of reactive oxygen species. In noncommunicable chronic diseases such as atherosclerosis and other cardiovascular pathologies, type 2 diabetes and metabolic syndrome, these modifications become systemic and are characterized by chronic inflammation and, in particular, "neuroinflammation" in the central nervous system. The processes associated with chronic inflammation are frequently grouped into "vicious circles" which are able to stimulate each other constantly amplifying the pathological events. These circles are evidently observed in Alzheimer's disease, atherosclerosis, type 2 diabetes, metabolic syndrome and, possibly, other associated pathologies. Furthermore, chronic inflammation in peripheral tissues is frequently concomitant to Alzheimer's disease. This is supposedly associated with some common genetic polymorphisms, for example, Apolipoprotein-E ε4 allele carriers with Alzheimer's disease can also develop atherosclerosis. Notably, in the transgenic mice expressing the recombinant mitochondria targeted catalase, that removes hydrogen peroxide from mitochondria, demonstrates the significant pathology amelioration and health improvements. In addition, the beneficial effects of some natural products from the xanthophyll family, astaxanthin and fucoxanthin, which are able to target the reactive oxygen species at cellular or mitochondrial membranes, have been demonstrated in both animal and human studies. We propose that the normalization of mitochondrial functions could play a key role in the treatment of neurodegenerative disorders and other noncommunicable diseases associated with chronic inflammation in ageing. Furthermore, some prospective drugs based on mitochondria targeted catalase or xanthophylls could be used as an effective treatment of these pathologies, especially at early stages of their development.

Inhibition of sigma-1 receptors substantially modulates GABA and glutamate transport in presynaptic nerve terminals.

Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric disorders and are a novel target for the treatment of such disorders. Sig-1R expression/activity deficits are linked to neurodegeneration, whereas the mechanisms mediated by Sig-1R are still unclear. Here, presynaptic [3H]GABA and L-[14C]glutamate transport was analysed in rat brain nerve terminals (synaptosomes) in the presence of the Sig-1R antagonist NE-100. NE-100 at doses of 1 and 10 µM increased the initial rate of synaptosomal [3H]GABA uptake, whereas 50 and 100 µM NE-100 decreased this rate, exerting a biphasic mode of action.Antagonists of GABAA and GABAB receptors, flumazenil and saclofen, respectively, prevented an increase in [3H]GABA uptake caused by 10 µM NE-100. L-[14C]glutamate uptake was decreased by 10-100 µM NE-100. A decrease in the uptake of both neurotransmitters mediated by NE-100 (50-100 µM) may have resulted from simultaneous antagonist-induced membrane depolarization, which was measured using the potential-sensitive fluorescent dye rhodamine 6G. The extracellular level of [3H]GABA was decreased by 1-10 µM NE-100, but that of L-[14C]glutamate remained unchanged. The tonic release of [3H]GABA measured in the presence of NO-711 was not changed by the antagonist, suggesting that NE-100 did not disrupt membrane integrity. The KCl- and FCCP-induced transporter-mediated release of L-[14C]glutamate was decreased by the antagonist; this may underlie the neuroprotective action of the antagonist in hypoxia/ischaemia. NE-100 (10-100 µM) decreased the KCl-evoked exocytotic release of [3H]GABA and L-[14C]glutamate, whereas the induction of the release of both neurotransmitters by the Ca2+ ionophore ionomycin was not affected by the antagonist; therefore, the mitigation of KCl-evoked exocytosis was associated with the NE-100-induced dysfunction of potential-dependent Ca2+ channels. Therefore, the Sig-1R antagonist can specifically act in an acute manner at the presynaptic level through the modulation of GABA and glutamate uptake, transporter-mediated release and exocytosis.

Plastic smoke aerosol: Nano-sized particle distribution, absorption/fluorescent properties, dysregulation of oxidative processes and synaptic transmission in rat brain nerve terminals.

Smoke from plastic waste incineration in an open air travels worldwide and is a major source of air pollution particulate matter (PM) that is very withstand to degradation and hazard to human health. Suspension of smoke aerosol components in water occurs during rains and fire extinguishing. Here, water-suspended plastic smoke aerosol (WPS) preparations suitable for biotesting were synthesized. It has been revealed using dynamic light scattering that WPS contained major nano-sized (∼30 nm) PM fraction, and this result was confirmed by electron microscopy. Optical absorption of WPS was in the UV region and an increase in λex led to a red-shift in fluorescence emission with a corresponding decrease in fluorescence intensity. WPS was analyzed in neurotoxicity studies in vitro using presynaptic rat cortex nerve terminals (synaptosomes). Generation of spontaneous reactive oxygen species (ROS) detected using fluorescent dye 2',7-dichlorofluorescein in nerve terminals was decreased by WPS (10-50 µg/ml) in a dose-dependent manner. WPS also reduced the H2O2-evoked ROS production in synaptosomes, thereby influencing cellular oxidative processes and this effect was similar to that for carbon nanodots. WPS (0.1 mg/ml) decreased the synaptosomal membrane potential and synaptic vesicle acidification in fluorimetric experiments. WPS (1.0 mg/ml) attenuated the synaptosomal transporter-mediated uptake of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H]GABA, respectively. This can lead to an excessive increase in the glutamate concentration in the synaptic cleft and neurotoxicity via over activation of ionotropic glutamate receptors. Therefore, WPS was neurotoxic and provoked presynaptic malfunction through changes of oxidative activity, reduction of the membrane potential, synaptic vesicle acidification, and transporter-mediated uptake of excitatory and inhibitory neurotransmitters in nerve terminals. In summary, synthesis and emission to the environment of ultrafine PM occur during combustion of plastics, thereby polluting air and water resources, and possibly triggering development of neuropathologies.

Age-Dependency of Levetiracetam Effects on Exocytotic GABA Release from Nerve Terminals in the Hippocampus and Cortex in Norm and After Perinatal Hypoxia.

Perinatal hypoxia can lead to multiple chronic neurological deficits, e.g., mental retardation, behavioral abnormalities, and epilepsy. Levetiracetam (LEV), 2S-(2-oxo-1-pyrrolidiny1) butanamide, is an anticonvulsant drug with proven efficiency in treating patients with focal and generalized seizures. Rats were underwent hypoxia and seizures at the age of 10-12 postnatal days (pd). The ambient level and depolarization-induced exocytotic release of [3H]GABA (γ-aminobutyric acid) were analyzed in nerve terminals in the hippocampus and cortex 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 norm and after perinatal hypoxia. LEV had no effects on the ambient [3H]GABA level. The latter increased during development and was further elevated after perinatal hypoxia in nerve terminals in the hippocampus during the whole period and in the cortex in young adults. Exocytotic [3H]GABA release from nerve terminals increased after perinatal hypoxia during development in the hippocampus and cortex, however this effect was preserved at all ages during blockage of GABA transporters by NO-711 in the hippocampus only. LEV realized its anticonvulsant effects at the presynaptic site through an increase in exocytotic release of GABA. LEV exerted more significant effect after perinatal hypoxia than in norm. Action of LEV was strongly age-dependent and can be registered in puberty and young adults, but the drug was inert at the infantile stage.

Degradative properties of two newly isolated strains of the ascomycetes Fusarium oxysporum and Lecanicillium aphanocladii

Two ascomycete strains were isolated from creosote-contaminated railway sleeper wood. By using a polyphasic approach combining morpho-physiological observations of colonies with molecular tools, the strains were identified as Fusarium oxysporum Schltdl. (IBPPM 543, MUT 4558; GenBank accession no. MG593980) and Lecanicillium aphanocladii Zare & W. Gams (IBPPM 542, MUT 242; GenBank accession no. MG593981). Both strains degraded hazardous pollutants, including polycyclic aromatic hydrocarbons, anthraquinone-type dyes, and oil. Oil was better degraded by F. oxysporum, but the aromatic compounds were better degraded by L. aphanocladii. With both strains, the degradation products of anthracene, phenanthrene, and fluorene were 9,10-anthraquinone, 9,10-phenanthrenequinone, and 9-fluorenone, respectively. During pollutant degradation, F. oxysporum and L. aphanocladii produced an emulsifying compound(s). Both fungi produced extracellular Mn-peroxidases, enzymes possibly involved in the fungal degradation of the pollutants. This is the first report on the ability of L. aphanocladii to degrade four-ring PAHs, anthraquinone-type dyes, and oil, with the simultaneous production of an extracellular Mn-peroxidase

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