Methamphetamine (METH) is a psychostimulant that causes neurologic and psychiatric abnormalities. Recent studies have suggested that its neurotoxicity may also result from its ability to compromise the blood-brain barrier (BBB). Herein, we show that METH rapidly increased the vesicular transport across endothelial cells (ECs), followed by an increase of paracellular transport. Moreover, METH triggered the release of tumor necrosis factor-alpha (TNF-α), and the blockade of this cytokine or the inhibition of nuclear factor-kappa B (NF-κB) pathway prevented endothelial dysfunction. Since astrocytes have a crucial role in modulating BBB function, we further showed that conditioned medium obtained from astrocytes previously exposed to METH had a negative impact on barrier properties also via TNF-α/NF-κB pathway. Animal studies corroborated the in vitro results. Overall, we show that METH directly interferes with EC properties or indirectly via astrocytes through the release of TNF-α and subsequent activation of NF-κB pathway culminating in barrier dysfunction.

The feeding ecology, growth and spatialetemporal abundance and distribution of Pomatoschistus microps (Krøyer, 1838) and Pomatoschistus minutus (Pallas, 1770) were studied between June 2003 and June 2004, based on beam trawl surveys and macrobenthic samples conducted in the Mondego estuary, Portugal. Polychaetes, molluscs and amphipods were the most important items in the diet of P. microps, while for P. minutus the dominant preys were polychaetes, mysids and decapods. Pomatoschistus microps' recruitment lasted for six months and was composed of three new cohorts per year. Pomatoschistus minutus had an uncommon long reproductive season, from April to November, and population segregation was found, corresponding to the two reproductive peaks. Populations of both species were composed mainly of 0-group individuals with sand gobies presenting a more extended life span. In the Mondego estuary, inter-and intra-specific spatial segregation occurred between the two species and between the 0C and 1C age groups of P. microps. Ó 2005 Elsevier Ltd. All rights reserved.Keywords: Pomatoschistus; diet overlap; life cycle; competition; resource partitioning; Mondego estuary IntroductionHigh fish abundance concentrated in particular areas, is a common feature in estuarine fish communities (Elliott et al., 2002). Consequently, co-occurrence of several similar morphological types (e.g. species of Soleidae, Mugilidae, Gobiidae) with overlap of ecological niches within the communities is expected. Spatial and temporal distribution, abundance patterns of fish assemblages as well as resource partitioning, are therefore, important and interesting issues for understanding the structure and dynamics of these communities (Cabral, 2000). Competition exists when the requirements of two or more individuals for a particular resource exceed the supply of that resource in the environment; or, if their demands do not exceed the supply, but they compete directly to obtain this resource. The study of diet is often used to evaluate competition between fish species (Elliott et al., 2002).Trophic and habitat segregation are among the most important aspects of resource partitioning in fish communities but it has been difficult to assess and prove the main force behind this process (Ross, 1986a). Evidences of coexistent Gobiidae species exhibiting vertical spatial segregation, temporal segregation in spawning and absence of niche shifts when one species was temporarily absent have been reported by NorteCampos and Temming (1994). The Gobiidae is a particularly successful family in both tropical and temperate seas, well represented in estuarine and freshwater environments. Gobiidae present more than 2000 species (Bouchereau and Guelorget, 1998) and virtually all gobies exhibit demersal eggs, male parental care and highly variable number of spawnings per season (Miller, 1984).In the Mondego estuary, four species of Gobiidae are present: Pomatoschistus microps (Krøyer, 1838), Pomatoschistus and Miller, 1966). Although it is usually an annual spe...

Nevertheless, from the management point of view, it could be stated that although some variations occurred due to environmental stress, the main core of the Mondego Estuary fish community remained relatively unchanged.

The nursery role of the Mondego estuary for marine fish species was studied between June 2003 and May 2004. The spatial and temporal distribution and abundance patterns of 0-group Dicentrarchus labrax (Linnaeus, 1758), Platichthys flesus (Linnaeus, 1758) and Solea solea (Linnaeus, 1758) were analyzed based on monthly sampling surveys in five stations along the estuarine gradient. Fishing took place during the night at low water of spring tides, using a 2 m beam trawl. The spatial patterns of estuarine colonization were different according to species. D. labrax showed a wider distribution, but the main nursery ground was the same as for S. solea. Highest densities of S. solea juveniles were found in oligohaline areas, with muddy bottoms and high benthic invertebrates availability, while P. flesus occurred mainly in the sandy uppermost areas. D. labrax was found in both these areas. Fish abundance in the estuary mainly reflected seasonal changes.

BackgroundExcitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent.MethodsIn current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1 +/− mouse.ResultsCortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism.ConclusionsOur data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be found.

Estuarine colonization, population structure and nursery functioning for 0-group sea bass (Dicentrarchus labrax), flounder (Platichthys flesus) and sole (Solea solea) in a mesotidal temperate estuary SummaryThe function of the Mondego estuary as a fish nursery habitat was investigated from June 2003 to June 2004 by comparing the timing of estuarine colonization with juveniles of sea bass Dicentrarchus labrax, flounder Platichthys flesus, and sole Solea solea, while also analysing their population structure, growth and diet composition. Differences in the onset of estuarine colonization were observed, since sole juveniles were the first to enter the estuary (in January), followed by flounder in April and sea bass in June. The estuarine population of these species consisted of several age-groups, although the majority of individuals belonged to age-groups 0 and 1. The growth rates determined for 0-group fish were within the range of those reported for other European estuarine systems. Some differences were also recognized regarding the timing of estuarine colonization and the length of the growing season. Diet of 0-group sea bass consisted mainly of Crustacea, Polychaeta and Mollusca. Flounder juveniles fed chiefly on Amphipoda (especially Corophium spp.), with Polychaeta, Isopoda and Decapoda also being common prey. The diet of 0-group sole was dominated by Polychaeta, with Amphipoda, Mollusca and Decapoda ranking highest, with other important benthic organisms also being present. Dietary overlap among these species was relatively low.

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The populations of Pomatoschistus minutus and Pomatoschistus microps were studied from June 2003 to May 2006 in the Mondego estuary, in order to understand the ability of these species to withstand environmental variability. During this period a severe drought occurred (2005), with consequent lower freshwater runoff and higher salinity incursion into the estuary. Occasional abnormal high water temperatures were observed in 2003 and 2005. The fish populations were sampled monthly along an estuarine gradient, from which population density, structure, growth and biomass production was assessed. Pomatoschistus minutus distributed mainly at the most saline downstream area, while P. microps distributed within the whole estuary, in accordance to the salinity and temperature tolerances for the species. A clear decrease in density and production was observed for P. minutus in the dry year, with non-expressive recruitments and the quick disappearance of the parental cohort. For P. microps, the decrease was not so pronounced. No direct effects were attributable to the salinity and temperatures variations (resulting from the drought and high temperatures). Yet, higher predation pressure on P. minutus hypothesis was raised, as the salinity incursion increased the piscivorous marine adventitious species in the downstream areas. Pomatoschistus microps benefited from a wider temperature and salinity range tolerance, allowing the species to occupy different areas in the estuary and by this seemed better able to cope with the environmental conditionings during the 3-year studied period.