Glutamatergic alterations in the cortex of genetic absence epilepsy rats

<p>Abstract</p> <p>Background</p> <p>In absence epilepsy, the neuronal hyper-excitation and hyper-synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an <it>in vivo </it>quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied <it>in vivo </it>glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured.</p> <p>Results</p> <p>Although extracellular concentrations of GABA and GLU in the cortex and thalamus were not significantly different between GAERS and NEC rats, cortical GLU uptake was significantly decreased in unrestrained awake GAERS. Expression of VGLUT2 and synaptophysin was increased in the cortex of GAERS compared to NEC rats, but no changes were observed in the thalamus.</p> <p>Conclusion</p> <p>The specific decrease in GLU uptake in the cortex of GAERS linked to synaptic changes suggests impairment of the glutamatergic terminal network. These data support the idea that a change in glutamatergic neurotransmission in the cortex could contribute to hyperexcitability in absence epilepsy.</p

Investigation of the antifouling constituents from the brown alga <i>Sargassum muticum</i> (Yendo) Fensholt

One of the most promising alternatives to toxic heavy metal-based paints is offered by the development of antifouling coatings in which the active ingredients are compounds naturally occurring in marine organisms and operating as natural antisettlement agents. Sessile marine macroalgae are remarkably free from settlement by fouling organisms. They produce a wide variety of chemically active metabolites in their surroundings, potentially as an aid to protect themselves against other settling organisms. In this study, a dichloromethane extract from the brown seaweed Sargassum muticum was tested in situ and, after 2 months of immersion, showed less fouling organisms on paints in which the extract was included, compared to paints containing only copper after 2 months of immersion. No barnacles or mussels have been observed on the test rack. Identification by NMR and GC/MS of the effective compound revealed the abundance of palmitic acid, a commonly found fatty acid. Pure palmitic acid showed antibacterial activity at 44 A µg mL-1, and also inhibited the growth of the diatom Cylindrotheca closterium at low concentration (EC50 = 45.5 A µg mL-1), and the germination of Ulva lactuca spores at 3 A µg mL-1. No cytotoxicity was highlighted, which is promising in the aim of the development of an environmentally friendly antifouling paint

Development of a triculture based system for improved benefit/risk assessment in pharmacology and human food

Development of a triculture based system for improved benefit/risk assessment in pharmacology and human food

Risks of Using Antifouling Biocides in Aquaculture

Biocides are chemical substances that can deter or kill the microorganisms responsible for biofouling. The rapid expansion of the aquaculture industry is having a significant impact on the marine ecosystems. As the industry expands, it requires the use of more drugs, disinfectants and antifoulant compounds (biocides) to eliminate the microorganisms in the aquaculture facilities. The use of biocides in the aquatic environment, however, has proved to be harmful as it has toxic effects on the marine environment. Organic booster biocides were recently introduced as alternatives to the organotin compounds found in antifouling products after restrictions were imposed on the use of tributyltin (TBT). The replacement products are generally based on copper metal oxides and organic biocides. The biocides that are most commonly used in antifouling paints include chlorothalonil, dichlofluanid, DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, Sea-nine 211®), Diuron, Irgarol 1051, TCMS pyridine (2,3,3,6-tetrachloro-4-methylsulfonyl pyridine), zinc pyrithione and Zineb. There are two types of risks associated with the use of biocides in aquaculture: (i) predators and humans may ingest the fish and shellfish that have accumulated in these contaminants and (ii) the development of antibiotic resistance in bacteria. This paper provides an overview of the effects of antifouling (AF) biocides on aquatic organisms. It also provides some insights into the effects and risks of these compounds on non-target organisms

Recherche et valorisation de principes actifs antifouling isolés à partir de trois macroalgues

L'interdiction de produits antifouling à base de TBT a contraint les entreprises productrices de peintures à trouver rapidement un substituant approprié afin de limiter le phénomène de biofouling sur les coques des bateaux. Les autres biocides utilisés dans les peintures antifouling ont également soulevé de nombreuses questions quant à leurs effets sur l'environnement marin. Une alternative peut être apportée par le développement de revêtements dans lesquels les ingrédients actifs seraient des composés issus d'organismes marins. Des études récentes confirment le potentiel d'ingrédients actifs à base d'extraits d'algues marines dans les préparations antifouling. Nous avons démontré au cours de notre étude que les extraits de Sargassum muticum (Heterokonta, Fucales), de Polysiphonia lanosa (Rhodobionta, Céramiales) et de Ceramium botryocarpum (Rhodobionta, Céramiales) présentent une activité antifouling intéressante comparés aux biocides utilisés actuellement dans les peintures antifouling. Des tests d'incorporation d'extraits d'algues bruts dans des revêtements antifouling ont été effectués durant les étés 2004 et 2005 dans le port de Lorient, et les premiers résultats sont prometteurs. La purification de l'extrait éthanol/dichlorométhane de S. muticum a permis d'isoler une fraction active dont la composition a été analysée. Les techniques de Spectrométrie de Masse, de Résonance Magnétique Nucléaire et de Chromatographie en Phase Gazeuse ont mis en évidence la présence d'acide palmitique et de dioctyl phthalate dans cette fraction. Les tests effectués sur les bactéries, microalgues et spores d'algues ont démontré l'efficacité antifouling de l'acide palmitique commercial.The ban of TBT-based antifouling products has forced the coating companies to find a suitable substitute to limit the development of fouling on ship hulls. The other organic biocides used in antifouling paints are suspected to have negative effects on the marine environment. An alternative exists with the development of antifouling coatings in which active ingredients would be isolated from marine organisms. Recent studies have demonstrated the potential of active compounds extracted from marine algae in antifouling paints. We have shown in our study that the extracts from Sargassum muticum (Heterokonta, Fucales), Polysiphonia lanosa (Rhodobionta, Ceramiales) and Ceramium botryocarpum (Rhodobionta, Ceramiales) present an interesting antifouling activity, which can be compared to the activity of the organic biocides used in antifouling paints. In situ tests have been conducted during the summer 2004 and 2005 in the harbour of Lorient, and the first results of crude extracts incorporated in coatings are promising. An active fraction has been isolated after the purification of the ethanol/dichloromethane extract from S. muticum. Mass Spectrometry, Nuclear Magnetic Resonance and Gas Chromatography technics have shown the presence of palmitic acid and dioctyl phthalate in the active fraction. The tests conducted on bacteria, microalgae and algae spores have demonstrated the antifouling efficiency of the palmitic acid.LORIENT-BU (561212106) / SudocSudocFranceF

REGULATIONS PHYSIOLOGIQUES ET PATHOLOGIQUES DES FONCTIONS ASTROCYTAIRES IMPLIQUEES DANS L'HOMEOSTASIE DU GABA ET DU GLUTAMATE (DOCTORAT (NEUROSCIENCES))

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

In vitro toxicity assessment of silver nanoparticles in the presence of phenolic compounds--preventive agents against the harmful effect?

The increasing commercial use of silver nanoparticles (Ag-NPs) will inevitably lead to elevated silver exposure and thus to potential human health complications. In this study the acute toxicity of Ag-NPs <20 nm alone and upon co-administration with food matrix component phenolic compounds (PCs) on the cell-based models of the gastrointestinal tract was investigated. An improved co-culture model of Caco-2 and RajiB cells was applied for more precise in vitro simulation of the gastrointestinal tract. The involvement of two major factors contributing to the toxicity of Ag-NPs, i.e. the release of Ag(+) and the induction of oxidative stress, was investigated. Ag-NPs were cytotoxic for Caco-2 cells with an EC50 of ca. 40 µg/ml. Ag-NPs led to oxidative stress starting from ca. 45 µg/ml. The epithelial barrier integrity disruption by Ag-NPs on Caco-2 cell mono- and co-cultures was established by decreased transepithelial electrical resistances and increased passages of Lucifer Yellow, a paracellular marker. Immunofluorescence staining demonstrated that Ag-NPs affect occludin and zonula occludens 1 distributions, suggesting the opening of tight junctions. Ag(+), corresponding to the release from Ag-NPs, demonstrated a partial contribution in the toxic parameters, induced by Ag-NPs. Two PCs, quercetin and kaempferol, partially protected the Caco-2 cells from Ag-NP-induced toxicity and maintained the epithelial barrier integrity, disrupted by NPs. No protective effect was observed for resveratrol. The protective effect could be beneficial and decrease the potential toxicity of ingested Ag-NPs. However, the precise mechanisms of barrier-integrity-destabilising action of Ag-NPs/Ag(+) and protective effect of PCs still require further elucidation