A Substrate Trapping Mutant Form of Striatal-Enriched Protein Tyrosine Phosphatase Prevents Amphetamine-Induced Stereotypies and Long-Term Potentiation in the Striatum

Background: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and I hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

Differential staining and microchromosomal variation in karyotypes of four Brazilian species of Tupinambinae lizards (Squamata : Teiidae)

Kayotypes of four neotropical teiid lizard species (Tupinambinae) were herein studied after conventional as well as silver staining and CBG-banding: Crocodilurus amazonicus (2n = 34), Tupinambis teguixin (2n = 36), Tupinambis merianae and Tupinambis quadrilineatus (2n = 38). The karyological data for T. quadrilineatus as well as those obtained using differential staining for all species were unknown until now. The karyotypes of all species presented 12 macrochromosomes identical in morphology, but differed in the number of microchromosomes: 22 in C. amazonicus, 24 in T. teguixin and 26 in T. quadrilineatus and T. merianae. The Ag-NOR located at the secondary constriction at the distal end of pair 2 is shared by all species, contrasting with the variability observed for this character in species of the related Teiinae. CBG-banding revealed a species-specific pattern in T. quadrilineatus with conspicuous interstitial C-blocks at the proximal region of the long arm of pair 4 and the whole heterochromatic short arm of pair 6. The karyological data reported here corroborates the relationship hypothesis obtained for Tupinambis based on molecular characters. T. teguixin presents the putative ancestral karyotype for the genus with 2n = 36 whereas T. merianae and T. quadrilineatus exhibit 2n = 38, due to an additional pair of microchromosomes.

Head shape evolution in Tropidurinae lizards: does locomotion constrain diet?

Different components of complex integrated systems may be specialized for different functions, and thus the selective pressures acting on the system as a whole may be conflicting and can ultimately constrain organismal performance and evolution. The vertebrate cranial system is one of the most striking examples of a complex system with several possible functions, being associated to activities as different as locomotion, prey capture, display and defensive behaviours. Therefore, selective pressures on the cranial system as a whole are possibly complex and may be conflicting. The present study focuses on the influence of potentially conflicting selective pressures (diet vs. locomotion) on the evolution of head shape in Tropidurinae lizards. For example, the expected adaptations leading to flat heads and bodies in species living on vertical structures may conflict with the need for improved bite performance associated with the inclusion of hard or tough prey into the diet, a common phenomenon in Tropidurinae lizards. Body size and six variables describing head shape were quantified in preserved specimens of 23 species, and information on diet and substrate usage was obtained from the literature. No phylogenetic signal was observed in the morphological data at any branch length tested, suggesting adaptive evolution of head shape in Tropidurinae. This pattern was confirmed by both factor analysis and independent contrast analysis, which suggested adaptive co-variation between the head shape and the inclusion of hard prey into the diet. In contrast to our expectations, habitat use did not constrain or drive head shape evolution in the group.

Phylogeny and ecology determine morphological structure in a snake assemblage in the central Brazilian Cerrado

To investigate the role of ecological and historical factors in the organization of communities, we describe the ecomorphological structure of an assemblage of snakes (61 species in six families) in the Cerrado (a savanna-like grassland) of Distrito Federal, Brazil. These snakes vary in habits, with some being fossorial, cryptozoic, terrestrial, semi-aquatic, or arboreal. Periods of activity also vary. A multivariate analysis identified distinct morphological groups associated with patterns of resource use. We report higher niche diversification compared to snakes in the Caatinga (a semi-arid region in northeastern Brazil), with fossorial and cryptozoic species occupying morphological space that is not occupied in the Caatinga. Monte Carlo permutations from canonical phylogenetic ordination revealed a significant phylogenetic effect on morphology for Colubridae, Colubrinae, Viperidae, Elapidae, and Boidae indicating that morphological divergence occurred in the distant past. We conclude that phylogeny is the most important factor determining structure of this Neotropical assemblage. Nevertheless, our results also suggest a strong ecological component characterizes a peculiar snake fauna.

Maintenance and differentiation of neural stem cells

The adult mammalian brain contains self-renewable, multipotent neural stem cells (NSCs) that are responsible for neurogenesis and plasticity in specific regions of the adult brain. Extracellular matrix, vasculature, glial cells, and other neurons are components of the niche where NSCs are located. This surrounding environment is the source of extrinsic signals that instruct NSCs to either self-renew or differentiate. Additionally, factors such as the intracellular epigenetics state and retrotransposition events can influence the decision of NSC`s fate into neurons or glia. Extrinsic and intrinsic factors form an intricate signaling network, which is not completely understood. These factors altogether reflect a few of the key players characterized so far in the new field of NSC research and are covered in this review. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 107-114 DOI:10.1002/wsbm:100

Assessing the impact of deforestation and climate change on the range size and environmental niche of bird species in the Atlantic forests, Brazil

Aim Habitat loss and climate change are two major drivers of biological diversity. Here we quantify how deforestation has already changed, and how future climate scenarios may change, environmental conditions within the highly disturbed Atlantic forests of Brazil. We also examine how environmental conditions have been altered within the range of selected bird species. Location Atlantic forests of south-eastern Brazil. Methods The historical distribution of 21 bird species was estimated using Maxent. After superimposing the present-day forest cover, we examined the environmental niches hypothesized to be occupied by these birds pre- and post-deforestation using environmental niche factor analysis (ENFA). ENFA was also used to compare conditions in the entire Atlantic forest ecosystem pre- and post-deforestation. The relative influence of land use and climate change on environmental conditions was examined using analysis of similarity and principal components analysis. Results Deforestation in the region has resulted in a decrease in suitable habitat of between 78% and 93% for the Atlantic forest birds included here. Further, Atlantic forest birds today experience generally wetter and less seasonal forest environments than they did historically. Models of future environmental conditions within forest remnants suggest generally warmer conditions and lower annual variation in rainfall due to greater precipitation in the driest quarter of the year. We found that deforestation resulted in a greater divergence of environmental conditions within Atlantic forests than that predicted by climate change. Main conclusions The changes in environmental conditions that have occurred with large-scale deforestation suggest that selective regimes may have shifted and, as a consequence, spatial patterns of intra-specific variation in morphology, behaviour and genes have probably been altered. Although the observed shifts in available environmental conditions resulting from deforestation are greater than those predicted by climate change, the latter will result in novel environments that exceed temperatures in any present-day climates and may lead to biotic attrition unless organisms can adapt to these warmer conditions. Conserving intra-specific diversity over the long term will require considering both how changes in the recent past have influenced contemporary populations and the impact of future environmental change.

Using ecological niche modelling to infer past, present and future environmental suitability for Leiopelma hochstetteri, an endangered New Zealand native frog

Leiopelma hochstetteri is an endangered New Zealand frog now confined to isolated populations scattered across the North Island. A better understanding of its past, current and predicted future environmental suitability will contribute to its conservation which is in jeopardy due to human activities, feral predators, disease and climate change. Here we use ecological niche modelling with all known occurrence data (N = 1708) and six determinant environmental variables to elucidate current, pre-human and future environmental suitability of this species. Comparison among independent runs, subfossil records and a clamping method allow validation of models. Many areas identified as currently suitable do not host any known populations. This apparent discrepancy could be explained by several non exclusive hypotheses: the areas have not been adequately surveyed and undiscovered populations still remain, the model is over simplistic; the species` sensitivity to fragmentation and small population size; biotic interactions; historical events. An additional outcome is that apparently suitable, but frog-less areas could be targeted for future translocations. Surprisingly, pre-human conditions do not differ markedly highlighting the possibility that the range of the species was broadly fragmented before human arrival. Nevertheless, some populations, particularly on the west of the North Island may have disappeared as a result of human mediated habitat modification. Future conditions are marked with higher temperatures, which are predicted to be favourable to the species. However, such virtual gain in suitable range will probably not benefit the species given the highly fragmented nature of existing habitat and the low dispersal ability of this species. (C) 2010 Elsevier Ltd. All rights reserved.

Exercise-induced plasticity of AMPA-type glutamate receptor subunits in the rat brain

The aim of this study was to analyze the plastic effects of moderate exercise upon the motor cortex (M1 and M2 areas), cerebellum (Cb), and striatum (CPu) of the rat brain This assessment was made by verifying the expression of AMPA type glutamate receptor subunits (GluR1 and GluR2/3) We used adult Wistar rats, divided into 5 groups based on duration of exercise training, namely 3 days (EX3), 7 days (EX7) 15 days (EX15) 30 days (EX30), and sedentary (S) The exercised animals were subjected to a treadmill exercise protocol at the speed of the 10 meters/min for 40 mm After exercise, the brains were subjected to immunohistochemistry and immunoblotting to analyze changes of GluR1 and GluR2/3, and plasma cortcosterone was measured by ELISA in order to verify potential stress induced by physical training Overall the results of immunohistochemistry and immunoblotting were similar and revealed that GluR subunits show distinct responses over the exercise periods and for the different structures analyzed In general, there was increased expression of GluR subunits after longer exercise periods (such as EX30) although some opposite effects were seen after short periods of exercise (Ex3) In a few cases biphasic patterns with decreases and subsequent increases of GluR expression were seen and may represent the outcome of exercise dependent, complex regulatory processes The data show that the protocol used was able to promote plastic GluR changes during exercise, suggesting a specific involvement of these receptors in exercise induced plasticity processes in the brain areas tested (C) 2010 Elsevier B V All rights reserved

Changes in extracellular levels of glutamate in the nucleus accumbens after ethanol-induced behavioral sensitization in adolescent and adult mice

Repeated administration of low doses of ethanol gradually increases locomotor responses to ethanol in adult Swiss mice. This phenomenon is known as behavioral sensitization. However, we have shown that adolescent Swiss mice show either behavioral tolerance or no sensitization after repeated ethanol injections. Although the mesolimbic dopamine system has been extensively implicated in behavioral sensitization, several studies have demonstrated an important role of glutamatergic transmission in this phenomenon. In addition, relatively few studies have examined the role of developmental factors in behavioral sensitization to ethanol. To examine the relationship between age differences in behavioral sensitization to ethanol and the neurochemical adaptations related to glutamate within nucleus accumbens (NAc), in vivo microdialysis was conducted in adolescent and adult Swiss mice treated with ethanol (1.8 g/kg) or saline for 15 days and subsequently challenged with an acute dose (1.8 g/kg) of ethanol 6 days later. Consistent with previous findings, only adult mice demonstrated evidence of behavioral sensitization. However, ethanol-treated adolescent mice demonstrated a 196.1 +/- 40.0% peak increase in extracellular levels of glutamate in the NAc after ethanol challenge in comparison with the basal values, whereas ethanol-treated adult mice demonstrated a 52.2 +/- 6.2% reduction in extracellular levels of glutamate in the NAc after ethanol challenge. These observations suggest an age-dependent inverse relationship between behavioral and glutamatergic responses to repeated ethanol exposure. (C) 2011 Elsevier Inc. All rights reserved.

Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice

Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.

Managing Seasonality in Tourism : Challenges and Opportunities for the Tourism Industry in Húsavík, Iceland

Seasonality is a common phenomenon in the tourism industry around the world. Húsavík, a town on the northern coast of Iceland, has experienced tremendous growth in tourism in recent years and is sometimes recognised as the „Whale Watching Capital of Europe‟. However, Húsavík faces extreme seasonality with high demand mainly during the summer months and limited or no demand at other times of the year. As is emphasised in the tourism literature and widely in practice, seasonality is frequently seen as a problem for the tourism industry which has to be tackled. Academic research has never before been done on seasonality in Húsavík and the aim of this thesis is to understand the nature of seasonality within the tourism industry in Húsavík and discover potential ways to reduce seasonality in Húsavík tourism. In order to fulfil the aim, qualitative semi-structured interviews were undertaken with six tourism managers in Húsavík to investigate their perceptions of seasonality and if and how it could be managed. The results confirmed that the peripheral location of the destination stimulates seasonality and it poses major economic challenges for tourism businesses in Húsavík. Managers would prefer a longer tourism season. Several recommendations were provided for how to reduce seasonality such as develop other attractions than whale watching, improve accessibility, focus marketing on seasons outside the summer, and offer winter packages for foreign and domestic tourists.

Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.