Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.
Reactive Oxidative Species (ROS) are produced during cellular metabolism and their amount is finely regulated because of negative consequences that ROS accumulation has on cellular functioning and survival. However, ROS play an important role in maintaining a healthy brain by participating in cellular signaling and regulating neuronal plasticity, which led to a shift in our understanding of ROS from being solely detrimental to having a more complex role in the brain. Here we use Drosophila melanogaster to investigate the influence of ROS on behavioral phenotypes induced by single or double exposure to volatilized cocaine (vCOC), sensitivity and locomotor sensitization (LS). Sensitivity and LS depend on glutathione antioxidant defense. Catalase activity and hydrogen peroxide (H2O2) accumulation play a minor role, but their presence is necessary in dopaminergic and serotonergic neurons for LS. Feeding flies the antioxidant quercetin completely abolishes LS confirming the permissive role of H2O2 in the development of LS. This can only partially be rescued by co-feeding H2O2 or the dopamine precursor 3,4-dihydroxy-L-phenylalanine (L-DA) showing coordinate and similar contribution of dopamine and H2O2. Genetic versatility of Drosophila can be used as a tool for more precise dissection of temporal, spatial and transcriptional events that regulate behaviors induced by vCOC.
Addiction is a multifactorial biological and behavioral disorder that is studied using animal models, based on simple behavioral responses in isolated individuals. A couple of decades ago it was shown that Drosophila melanogaster can serve as a model organism for behaviors related to alcohol, nicotine and cocaine (COC) addiction. Scoring of COC-induced behaviors in a large group of flies has been technologically challenging, so we have applied a local, middle and global level of network-based analyses to study social interaction networks (SINs) among a group of 30 untreated males compared to those that have been orally administered with 0.50 mg/mL of COC for 24 hours. In this study, we have confirmed the previously described increase in locomotion upon COC feeding. We have isolated new network-based measures associated with COC, and influenced by group on the individual behavior. COC fed flies showed a longer duration of interactions on the local level, and formed larger, more densely populated and compact, communities at the middle level. Untreated flies have a higher number of interactions with other flies in a group at the local level, and at the middle level, these interactions led to the formation of separated communities. Although the network density at the global level is higher in COC fed flies, at the middle level the modularity is higher in untreated flies. One COC specific behavior that we have isolated was an increase in the proportion of individuals that do not interact with the rest of the group, considered as the individual difference in COC induced behavior and/or consequence of group influence on individual behavior. Our approach can be expanded on different classes of drugs with the same acute response as COC to determine drug specific network-based measures and could serve as a tool to determinate genetic and environmental factors that influence both drug addiction and social interaction.
Selenium (Se) is an essential element for human health in trace amounts but is harmful in excess. Most plants contain a fairly low Se and crop Se supplements ensure adequate levels for human nutritional needs. Food is the primary source of Se for humans and due to differences in eating habits, its intake varies considerably. In the human body, selenium deficiency can lead to diseases of the endocrine, musculoskeletal, cardiovascular, reproductive, nervous and immune systems. Selenium is an important ingredient in glutathione peroxidase, the main cellular antioxidant enzyme, which can convert free radicals into peroxides, while vitamin E removes free radicals and neutralizes their potentially harmful effects. Excessive amounts of selenium in the human diet are considered toxic, causing liver and kidney damage, blood clotting, heart and liver necrosis, skin lesions, nausea, vomiting, and loss of hair and nails. Semiconducting properties of Se make it of special value for industry. Selenium is a rare element on the planet, and is a non-renewable resource due to its non-efficient and difficult recycling. Except of coal, which is commonly enriched in Se, there are no ores which could be mined for it. Herewith, the world's scarce Se resources need a careful management, monitoring, recycling, and stockpiling for future generations. The first part of this review outlines selenium concentrations in soil, water, and plants in terms of essential and toxicological effects on animals and humans, while the second part briefly overviews novel biotechnological methods of bioremediation of environmental selenium.
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