Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor

Previous pharmacological studies have indicated the possible existence of functional interactions between μ-, δ- and κ-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of δ- and κ-opioid receptors in mice lacking the μ-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPγS binding and adenylyl cyclase inhibition showed that functional coupling of δ- and κ-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[d-penicillamine2,d-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR −/− mice. δ-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR −/− mice. Analgesic and respiratory responses produced by the selective κ-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of δ- and κ-receptor signaling properties in mice lacking μ-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the κ-agonist further suggest that the κ-receptor mainly acts independently from the μ-receptor in vivo. Reduced δ-analgesia and the absence of δ-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between μ-receptors and central δ-receptors in specific neuronal pathways.

Lack of CB1 receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behavior and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared to wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the dorsal raphe nucleus, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an overexpression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the dorsal raphe nucleus by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.

CB1 cannabinoid receptor modulates MDMA acute responses and reinforcement

Background: 3, 4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endocannabinoid system is involved in the addictive processes induced by different drugs of abuse. However, the role of this system in the pharmacological effects of MDMA has not been yet clarified.Methods: Locomotion, body temperature and anxiogenic-like responses were evaluated after acute MDMA administration in CB1 knockout mice. Additionally, MDMA rewarding properties were investigated in the place conditioning and the intravenous self-administration paradigms. Extracellular levels of DA in the nucleus accumbens were also analyzed after a single administration of MDMA by in vivo microdialysis. Results: Acute MDMA administration increased locomotor activity, body temperature and anxiogenic-like responses in wild type mice, but these responses were lower or abolished in knockout animals. MDMA produced similar conditioned place preference and increased dopamine extracellular levels in the nucleus accumbens in both genotypes. Nevertheless, CB1 knockout mice failed to self-administer MDMA at any of the doses used. Conclusions: These results indicate that CB1 cannabinoid receptors play an important role in the acute prototypical effects of MDMA, and are essential in the acquisition of an operant behavior to self-administer this drug.

MDMA attenuates THC withdrawal syndrome in mice

3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Δ9-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC, and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. Both, chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.

THC prevents MDMA neurotoxicity in mice

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this process.

La meiosi

La unitat didàctica s’inicia amb una seqüència per emfatitzar la importància del llenguatge en ciències, contextualitzada en el desxiframent dels jeroglífics egipcis i en el mètode hipotètic-deductiu que s’utilitzà per a desxifrar-los. Aquest, serà el fil conductor per introduir la meiosi, ara emmarcada en un cas de Síndrome de Down, determinat en el cariotip de l’embrió d’una parella que rep el diagnòstic prenatal d’un equip investigador. Amb activitats proposades durant les sis sessions l’alumne haurà d’ aprendre a identificar evidències, a justificar proves a partir de continguts teòrics, i a formular hipòtesis a partir d’un cas; a explicitar el procés amb recursos simbòlics i visuals; a comprendre’n la funcionalitat i a caracteritzar-ne les fases. S’utilitzen eines de regulació tals com el treball cooperatiu i la coavaluació, així com pautes i bases d’orientació. També es treballen les idees prèvies i l’atenció a la diversitat present a l’aula.

Trets d'oralitat en la novel·la Effi Briest de Theodor Fontane i la seva traducció al català i al castellà. La traducció de la partícula nun

L’objectiu del treball és mostrar la problemàtica de la traducció d’un element característic de la llengua parlada en l’alemany al català i al castellà, i determinar quines tècniques s’utilitzen de manera més freqüent i efectiva per a realitzar-la. L’element d’estudi és la partícula nun, molt freqüent en la novel•la Effi Briest de Theodor Fontane. Una de les funcions d’aquesta partícula és l’expressió de modalitat.Després d’una aproximació a l’oralitat fingida es fa referència a l’autor i a la novel•la, i es mostren els trets d’oralitat que aquesta conté. Les diverses taules permeten justificar l’objecte del treball i realitzar les hipòtesis i valoracions sobre el funcionament de la partícula i la seva traducció al català i al castellà.El treball finalitza amb l’anàlisi comparativa de la traducció d’aquells fragments d’un dels capítols de la novel•la on apareix la partícula. L’anàlisi comprèn una part descriptiva i la crítica de les traduccions.

La Contribución al desarrollo humano de las políticas públicas de TIC para la educación en los países del Cono Sur (Argentina, Chile y Uruguay)

Aquesta investigació estudia la contribució al Desenvolupament Humà de les polítiques publiques de TIC per a l’Educació als països del Cono Sur (Argentina, Xile i Uruguai). Aquests països van al capdavant de la regió en temes de TIC, Educació i Desenvolupament, així doncs l’objectiu final es veure si les polítiques publiques que enfatitzen en aspectes vinculats al Desenvolupament Humà afavoreixen el desenvolupament del països. Per a això s’han analitzat les Agendes Digitals dels països seleccionats en base a una matriu d’anàlisi creada específicamente per a aquesta investigación i construïda amb indicadors vinculats al Desenvolupament Humà

Standards and specifications to manage accessibility issues in e-learning

Standards and specifícations to manage accessibility issues in e-learning

L'Impuls de la marca-ciutat Barcelona com a mecanisme de reactivació econòmica

La recerca tracta sobre els diferents mecanismes que les ciutats i les regions utilitzen per millorar la seva imatge. En aquest sentit, el treball se centra en la marca-ciutat, el màrqueting de ciutats i els diferents models de comunicació emprats per exaltar la reputació dels territoris. Pel que fa la segona part de la recerca, consisteix en l’estudi de la marca-ciutat Barcelona en els àmbits dels negocis, la societat del coneixement, el turisme, la sostenibilitat i la qualitat de vida i la cultura. Per tant, el propòsit d’aquesta recerca és comprendre quines accions desenvolupen els principals actors per incentivar els negocis a Barcelona, descobrir quines iniciatives s’han pres per potenciar l’economia del coneixement, el turisme, la sostenibilitat i la qualitat de vida i la indústria cultural a la ciutat de Barcelona

La contractació de serveis externs: un recurs imprescindible per a les biblioteques escolars

El Servei de Biblioteques Escolars L'Amic de Paper ofereix als centres educatius recursos orientats a donar suport a l'organització, manteniment i dinamització de les biblioteques escolars per tal de millorar la situació en què es troben, amb l'objectiu final d'aconseguir que aquestes siguin el centre de formació i informació que la comunitat educativa necessita.

Literatura contra enfermedad: la biblioterapia

La biblioterapia es un método terapéutico interdisciplinario que intenta paliar la vulnerabilidad producida a raíz de una enfermedad mediante la literatura imaginativa. El objetivo del póster es dar a conocer la biblioterapia como terapia alternativa para mejorar la calidad de vida de los niños hospitalizados. Se propone una actuación transversal en la que participen los profesionales sanitarios (ejercen un control sobre el comportamiento de los participantes a través del estudio de sus procesos psíquicos y cognitivos), los bibliotecarios (buscan y seleccionan el material idóneo en cada caso), y las familias (colaboran activamente en su realización).

Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP.

Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and noncoated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgito-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(AWA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-NWASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP¿dependent manner.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.