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O consumo repetido de drogas, nomeadamente opióides, conduz ao desenvolvimento de dependência. Entre os mecanismos envolvidos neste processo, comuns à maioria das drogas de abuso, destaca-se a activação da neurotransmissão dopaminérgica em zonas específicas do cérebro. O metabolismo oxidativo da dopamina confere-lhe um potencial neurotóxico devido à formação de espécies reactivas de oxigénio, nomeadamente peróxido de hidrogénio (H2O2). Neste trabalho avaliou-se o efeito da exposição crónica de células PC12 à “heroína de rua” ou ao H2O2 na resposta destas células a uma exposição aguda a estes compostos, em comparação com células PC12 “naïve” (sem exposição prévia aos compostos). As células cronicamente expostas à heroína ou ao H2O2 apresentaram-se parcial ou totalmente resistentes, respectivamente, a uma exposição aguda ao H2O2. Este efeito correlacionou-se com a manutenção dos níveis de ATP após exposição aguda ao H2O2, em contraste com as células “naïve”. Para além disso, observou-se que a viabilidade das células cronicamente expostas à heroína e ao H2O2 era mais afectada pela heroína, comparativamente às células “naïve”. Esta sensibilização poderá ser explicada pelo aumento da acumulação extracelular de dopamina, induzida por estes compostos. Por outro lado, a exposição aguda à heroína de células já cronicamente expostas a esta droga de abuso induziu uma maior susceptibilidade comparativamente a células cronicamente expostas ao H2O2. Esta observação poderá ser explicada por um decréscimo dos níveis intracelulares de ATP e ADP induzido pela incubação crónica com “heroína de rua”, o que indicia um compromisso energético destas células. Em resumo, a exposição crónica à “heroína de rua” altera os níveis energéticos celulares, os níveis extracelulares de dopamina e a resposta a estímulos citotóxicos, evidenciando-se o papel nocivo do consumo regular desta droga por toxicodependentes.

Cocaine is a psychostimulant drug with sympathomimetic properties that is widelyabused. In the central nervous system, cocaine interacts with monoaminergic systems,which mediate many of the drug's effects. However, the interaction with thedopaminergic system is the main cause of cocaine's addictive effects. Cocaine shareschemical similarities with dopamine and binds to the dopamine transporter at the plasmamembrane of dopaminergic terminals, blocking dopamine re-uptake, resulting inincreased synaptic dopamine. Excess dopamine levels may induce oxidative stressthrough dopamine auto-oxidation, generating reactive oxygen species. Cocaine alsoaffects glutamate levels and the expression of glutamate receptors, which may mediateexcitotoxic cell damage. Interactions with these neurotransmission systems may underliecocaine neurotoxicity.Cocaine has also been shown to impair mitochondrial function in several models,namely through the inhibition of mitochondrial respiratory chain complex I and mayinduce the activation of mitochondrial apoptotic pathways. Cocaine is frequently coabusedwith heroin in a combination known as speedball. Indeed, heroin may modulate ormodify cocaine's effects.A chemical interaction between cocaine and morphine was found in drug mixturessimilar to those used by speedball abusers, which may have a specific neurotoxic profile.In addition, cocaine abuse shares some common aspects with neurodegenerativedisorders such as Parkinson's disease (PD), which also involves a dysfunction in thedopamine system. Thus, although neurotoxicity of cocaine may not be very pronounced,it may underlie brain dysfunction in cocaine and poly-drug abusers, which may predispose the brain to the development of neurodegenerative diseases.

Insulin signaling in central nervous system (CNS) has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD) considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

18 p., 5 figures, 1 table and references Photoperiod and temperature are known as the main synchronizers of seasonal reproduction in fish. This paper studied the role of photoperiod on the synchronization of F1 Senegal sole reproduction rhythms. Fish were maintained under constant short-photoperiod (9L:15D) from the winter solstice onwards (experimental group) or under naturally-changing photoperiod (control group), and water temperature naturally oscillated in both groups. Blood samples were collected during the reproduction season at pre-spawning (March), spawning (April) and post-spawning (May) to determine the endocrine status. Spawning events and egg quality parameters were also monitored. The results revealed a significant increase in nocturnal melatonin concentration from March to May in the control group, while in the experimental group such seasonal change did not occur. As to plasma levels of vitellogenin, testosterone, estradiol and 11keto-testosterone, differences between groups were found mostly in March, while in April and May levels were often similar. Spawning was observed in both groups, although the experimental group started slightly earlier and also finished earlier than the control group, perhaps as a result of the increase in sex steroids and VTG observed at pre-spawning. Briefly, reproduction rhythms persisted in the absence of the natural lengthening of photoperiod, although photoperiod manipulation altered the seasonal modulation of melatonin, increased sex steroids and vitellogenin at pre-spawning, and slightly advanced the timing of spawning. This work was financed by the MEC (project Reprosolea AGL2004-07984-CO2-01/ACU granted to FJSV and project AGL2006-13777-C03-01 to EM) and by SENECA (Project 05690/PI/07 to FJSV). CO received a FPI Fellowship from the MEC.

Chronobiology is the field of science which studies the biological rhythms and the mechanisms by which the organisms adapt to a constantly changing environment. Animals synchronize their rhythms with environmental cycles choosing the most suitable moment to feed, reproduce or be active, thereby optimizing biological processes. In fish, the study of circadian activity and feeding rhythms has been profusely investigated lately; however, reproduction rhythms are often neglected. Fish species reproduce once a year around a species specific season, but many of them can also present lunar reproduction rhythms and may even select the best moment of the day to spawn (Oliveira & Sánchez-Vázquez 2009). Knowing the moment of the day spawning occurs can improve egg collection protocols and provide insides about time of ovulation. This kind of knowledge can be very useful for gamete collection and in vitro fertilization procedures. In fact, for species like red snapper, red sea bream or bambooleaf wrasse, daily maturation rhythms have been observed (Matsuyama et al. 1988, 1998; Jackson et al. 2006). Thus the objective of this work is to review the evidences of daily rhythms of reproduction in teleost species (e.g. Senegal sole, Solea senegalensis, gilthead seabream, Sparus aurata, European sea bass, Dicentrarchus labrax, white seabream, Diplodus sargus, and zebrafish, Danio rerio), highlighting the importance of the time of day in gamete studies., This research was funded by the MEC project Reprosolea, AGL 2004-07984-C02-01, and by SENECA Project 05690/PI/07 both granted to FJSV, as well as by ProSpawn project (FP7/SME/2008/1) conceded to MTD. CO is supported by a Post Doctoral grant from the Portuguese Ministry of Science and Technology (SFRH/BPD/63933/2009) co-founded by POPH - QREN - Tipologia 4.1 (FEDER and MCTES). Trabajo presentado en el 3rd International Workshop on Biology of Fish Gametes, celebrado en Budapest del 7 al 9 de septiembre de 2011.

Ponencia presentada en el Aquaculture Europe Annual Meeting celebrado en Oporto del 5 al 8 de octubre de 2010

In this study, we evaluated the effect of lipoic acid (LA) and N-acetyl cysteine (NAC) on oxidative [4-hydroxy-2-nonenal, N(epsilon)-(carboxymethyl)lysine and heme oxygenase-1] and apoptotic (caspase 9 and Bax) markers in fibroblasts from patients with Alzheimer disease (AD) and age-matched and young controls. AD fibroblasts showed the highest levels of oxidative stress, and the antioxidants, lipoic acid (1 mM) and/or N-acetyl cysteine (100 microM) exerted a protective effect as evidenced by decreases in oxidative stress and apoptotic markers. Furthermore, we observed that the protective effect of LA and NAC was more pronounced when both agents were present simultaneously. AD-type changes could be generated in control fibroblasts using N-methylprotoporphyrin to inhibit cytochrome oxidase assembly indicating that the the oxidative damage observed was associated with mitochondrial dysfunction. The effects of N-methylprotoporphyrine were reversed or attenuated by both lipoic acid and N-acetyl cysteine. These data suggest mitochondria are important in oxidative damage that occurs in AD. As such, antioxidant therapies based on lipoic acid and N-acetyl cysteine supplementation may be promising

Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and that insulin has a neuroprotective role in oxidative stress conditions. In this study, we evaluated the in vitro effect of insulin in the susceptibility to oxidative stress and in the transport of the amino acid neurotransmitters γ-aminobutyric acid (GABA) and glutamate in a synaptosomal fraction isolated from male type 2 diabetic Goto-Kakizaki (GK) rat brain cortex. The ascorbate/Fe2+-induced increase in thiobarbituric acid reactive substances (TBARSs) was similar in Wistar and GK rats and was not reverted by insulin (1 μmol/l), suggesting that other mechanisms, rather than a direct effect in membrane lipid peroxidation, may mediate insulin neuroprotection. Diabetes did not affect GABA and glutamate transport, despite the significant decrease in membrane potential and ATP/ADP ratio, and insulin increased the uptake of both GABA and glutamate in GK rats. Upon oxidation, there was a decrease in the uptake of both neurotransmitters and an increase in extrasynaptosomal glutamate levels and in ATP/ADP ratio in GK rats. Insulin treatment reverted the ascorbate/Fe2+-induced decrease in GABA accumulation, with a decrease in extrasynaptosomal GABA. These results suggest that insulin modulates synaptosomal GABA and/or glutamate transport, thus having a neuroprotective role under oxidizing and/or diabetic conditions

Genetic factors play a major role in the etiology of schizophrenia and disturbances of serotonergic pathways have been implicated in this disorder. The aim of the present study was to examine genetic association between schizophrenia and polymorphisms in the 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) autoreceptor genes in ninety trios from Portugal. No association or linkage disequilibrium was obtained between schizophrenia and 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT). Concerning 5-HT1Dbeta autoreceptor gene, also negative results was obtained in the analysis of the haplotypes with transmit. Thus, our data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population. © 2004 Wiley-Liss, Inc.

Alterations in dopaminergic system have been implicated in the pathophysiology of this disease for many years, and this study was performed to assess the possible involvement of the dopamine D4 receptor (DRD4) gene polymorphisms either in the 5prime upstream or in the coding regions, in the etiology of schizophrenia. The approach included an association study with 90 Portuguese trios by doing the analysis of the individual alleles and the haplotypes. For the polymorphisms in the 5prime upstream region (-C616G and -C521T) and in the coding region (48 bp repeat) of the DRD4 gene, negative results were obtained with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT), as well as transmit. These data suggest that polymorphisms (-C616G, -C521T, and 48 bp repeat) at the DRD4 gene do not have a minor effect in the susceptibility to schizophrenia in our sample. © 2003 Wiley-Liss, Inc.

In this study, we investigated the structure-activity relationship of four flavonoids, i.e. eriodictyol, luteolin, quercetin, and taxifolin, in cultured retinal cells after ascorbate/Fe2+-induced oxidative stress. The relative order of antioxidant efficacy, determined by the thiobarbituric acid method, was the following: eriodictyol > quercetin > luteolin > taxifolin. Upon preincubation, the flavonoids were also effective in reducing the extent of lipid peroxidation. Oxidative stress, determined by the changes in fluorescence of 2',7'-dichlorodihydrofluorescein, was also decreased in the presence of the flavonoids, showing the following order of antioxidant efficacy: eriodictyol > taxifolin [approximate] quercetin > luteolin. Ascorbate/Fe2+-induced oxidative stress or incubation in the presence of the flavonoids did not significantly affect the viability of retinal cells. We also evaluated the degree of membrane partition of the flavonoids. In this system, the results strongly suggest that the higher antioxidant activity of the flavonoids is not correlated with the presence of a double bond at C2-C3 and/or a hydroxyl group at C3 on the C ring, but rather may depend on the capacity to inhibit the production of reactive oxygen species to interact hydrophobically with membranes. Eriodictyol was shown to be the most efficient antioxidant in protecting against oxidative stress induced by ascorbate/Fe2+ in the retinal cells. http://www.sciencedirect.com/science/article/B6T4P-433NTS7-D/1/f92e0342be119c0ec4f7a436566bc7fd