Adult hippocampal neurogenesis is a unique example of structural plasticity, the functional role of which has been a matter of intense debate. New transgenic models have recently shown that ...neurogenesis participates in hippocampus-mediated learning. Here, we show that transgenic animals, in which adult hippocampal neurogenesis has been specifically impaired, exhibit a striking increase in anxiety-related behaviors. Our results indicate that neurogenesis plays an important role in the regulation of affective states and could be the target of new treatments for anxiety disorders.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance ...between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2
signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Defining the drug-induced neuroadaptations specifically associated with the behavioral manifestation of addiction is a daunting task. To address this issue, we used a behavioral model that ...differentiates rats controlling their drug use (Non-Addict-like) from rats undergoing transition to addiction (Addict-like). Dysfunctions in prefrontal cortex (PFC) synaptic circuits are thought to be responsible for the loss of control over drug taking that characterizes addicted individuals. Here, we studied the synaptic alterations in prelimbic PFC (pPFC) circuits associated with transition to addiction. We discovered that some of the changes induced by cocaine self-administration (SA), such as the impairment of the endocannabinoid-mediated long-term synaptic depression (eCB-LTD) was similarly abolished in Non-Addict- and Addict-like rats and thus unrelated to transition to addiction. In contrast, metabotropic glutamate receptor 2/3-mediated LTD (mGluR2/3-LTD) was specifically suppressed in Addict-like rats, which also show a concomitant postsynaptic plasticity expressed as a change in the relative contribution of AMPAR and NMDAR to basal glutamate-mediated synaptic transmission. Addiction-associated synaptic alterations in the pPFC were not fully developed at early stages of cocaine SA, when addiction-like behaviors are still absent, suggesting that pathological behaviors appear once the pPFC is compromised. These data identify specific synaptic impairments in the pPFC associated with addiction and support the idea that alterations of synaptic plasticity are core markers of drug dependence.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The endocannabinoid system is a potential pharmacotherapy target for obesity. However, the role of this system in human food intake regulation is currently unknown.
To test whether circulating ...endocannabinoids might functionally respond to food intake and verify whether these orexigenic signals are deregulated in obesity alongside with anorexigenic ones, we measured plasma anandamide (AEA), 2-arachidonoylglycerol (2-AG) and peptide YY (PYY) changes in response to a meal in 12 normal-weight and 12 non-diabetic, insulin-resistant obese individuals.
Both normal-weight and obese subjects had a significant preprandial AEA peak. Postprandially, AEA levels significantly decreased in normal-weight, whereas no significant changes were observed in obese subjects. Similarly, PYY levels significantly increased in normal-weight subjects only. No meal-related changes were found for 2-AG. Postprandial AEA and PYY changes inversely correlated with waist circumference, and independently explained 20.7 and 21.3% of waist variance. Multiple regression analysis showed that postprandial AEA and PYY changes explained 34% of waist variance, with 8.2% of the variance commonly explained.
These findings suggest that AEA might be a physiological meal initiator in humans and furthermore show that postprandially AEA and PYY are concomitantly deregulated in obesity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and ...benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ
-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IntroductionBipolar disorder (BD) is a chronic and recurrent mental condition characterized by mood fluctuations between hypomania or mania and depression, with high level of burden and mortality ...rates (Hayes et al., 2015). Subsyndromal mood symptoms, including residual depression, mania and/or anxiety, are major risk factors for episodic relapses after mood stabilisation (Samalin et al., 2016). A psychological protective mechanism against the occurrence of these maladaptative mood symptoms is dispositional mindfulness (DM). DM refers to paying purposeful attention to present moment experiences with a curious, non-judgmental and accepting attitude (Radford et al., 2014). DM has been barely assessed in BD and there is very little evidence on the relationship between DM, residual mood symptoms and quality of lifeObjectivesTo explore associations between DM, residual mood symptoms and quality of life in individuals with BDMethodsAfter informed consent, a total of 94 adults (Mean age= 45.57 years, 41.50% Male) with diagnosis of BD according to DSM-5 criteria, in full or partial remission,were recruited from the Bipolar and Depressive Disorders Unit at the Hospital Clinic of Barcelona. The ethical committee approved this study. Dispositional mindfulness was assessed using the Mindfulness Attention Awareness Scale (MAAS).The presence of residual depressive symptoms was assessed with the Hamilton Depression Rating Scale (HDRS), residual mania symptoms were assessed with the Young Mania Rating Scale(YMRS), and anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale (HAM-A). The subjective quality of life was assessed with the Quality of Life in Bipolar Disorder Questionnaire (QoL-BD). Pearson correlations were carried out and the level of significance was set at p<0.05ResultsDM was negatively related to residual depressive symptoms (r= -0.283; p=0.009) and to anxiety symptoms (r=-0.345; p<0.001), and positively related to quality of life (r=0.433; p<0.001), but not related to residual manic symptoms in BDConclusionsOur preliminary data suggest that BD patients with higher levels of DM may experience less depressive and anxiety subsyndromal symptoms and perceived higher quality of life. No associations were detected regarding mania symptoms. These findings support the use of mindfulness training as an adjunct therapy to pharmacotherapy to reduce residual mood symptoms and improve quality of life in patients with BDDisclosure of InterestNone Declared
The hippocampal formation, to which new neurons are added on a daily basis throughout life, is important in spatial learning. Surviving de novo produced cells integrate into the functional circuitry, ...where they can influence both normal and pathological behaviors. In this study, we examined the effect of the water-maze (a hippocampal-dependent spatial task) on neurogenesis. Learning in this task can be divided into two phases, an early phase during which performance improves rapidly, and a late phase during which asymptotic levels of performance are reached. Here we demonstrate that the late phase of learning has a multifaceted effect on neurogenesis depending on the birth date of new neurons. The number of newly born cells increased contingently with the late phase and a large proportion of these cells survived for at least 4 weeks and differentiated into neurons. In contrast, late-phase learning decreased the number of newly born cells produced during the early phase. This decline in neurogenesis was positively correlated with performance in the water-maze. Thus, rats with the highest de novo cell number were less able to acquire and use spatial information than those with low numbers of new cells. These results show that learning has a complex effect on hippocampal neurogenesis, and reveals a novel mechanism through which neurogenesis may influence normal and pathological behaviors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Environmental experiences have an important effect on the sensitivity of an individual to drugs of abuse. Studies of drug self-administration in laboratory animals have shown that both physical and ...psychological stressors facilitate the acquisition of drug self-administration, probably by increasing the reinforcing efficacy of drugs of abuse. Stressors also facilitate the reinstatement of drug taking even after prolonged periods of withdrawal. The adrenal hormones, glucocorticoids, which increase the sensitivity of mesencephalic dopaminergic neurones to drugs, seem to be one of the biological substrates of the effects of stress on the propensity to develop drug intake. In this review, Pier Vincenzo Piazza and Michel Le Moal discuss theories of drug abuse, the influence of different stressful experiences on drug self-administration and their possible mechanisms of action.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
While many Latin teachers are successfully implementing Comprehensible Input-based practices1 in their classrooms, plenty of teachers are hesitant to do so - and for good reason. One need only follow ...the discussions on the various blogs and Facebook groups dedicated to CI-based practices to see a predictable arc that goes from enthusiastic implementation to giving up and falling back on previous practices. Teachers who are attracted to CI-based practices are often those who also are frustrated with the traditional textbooks and curricula, and so a change in methods is often accompanied by a loosening of a traditional unit structure, or even the daily and weekly structure of a traditional language classroom. To do this, however, is to confuse the content of classroom instruction with the practices that contain them, the latter being an important element of classroom management.
Ageing is accompanied by an alteration of spatial memory, a decline in hippocampal neurogenesis and a dysregulation of the hypothalamic–pituitary axis (HPA) leading to elevated levels of circulating ...corticosterone. However, the role of the HPA axis in age-related decline in cognitive functions and in neurogenesis decline remains unclear. We found that suppression of glucocorticoids secretion from midlife to the rest of the animals’ life increases neurogenesis in old animals and prevents the emergence of age-related memory disorders. Reciprocally, aged rats with a chronic upregulation of the HPA axis exhibit not only spatial memory impairments but also very low levels of hippocampal cell proliferation and survival. Altogether, these results indicate that the extent of lifetime exposure to glucocorticoids determines the extent of age-related decline in hippocampal neurogenesis and consequently age-related cognitive dysfunctions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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