322,992 research outputs found
The politics of structural refoRms : social and industrial policy change in Italy and Japan
No full textItaly’s labour policy and policymaking in the crisis : from distributive coalitions to the shadow of hierarchy
No full textTargeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia.
No full textAntipsychotics are the mainstay of schizophrenia treatment. However, approximately one third of schizophrenic patients do not respond or respond poorly to antipsychotics. Therefore, there is a need for new approaches that can improve schizophrenia treatment significantly. Promising strategies arise from the modulation of glutamatergic system, according to its proposed involvement in schizophrenia pathogenesis. In this review, we critically updated preclinical and clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines, mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results in animal models mimicking the pathophysiology of psychosis, mainly believed to be responsible of negative and cognitive symptoms, and predicting antipsychotic-like activity of these compounds; and 2) clinical efficacy in open-label and double-blind trials. Albeit promising preclinical findings for virtually all compounds, clinical efficacy has not been confirmed for D-cycloserine. Contrasting evidence has been reported for glycine and D-serine, that may however have a role as add-on agents. More promising results in humans have been found for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro-cognitive agents, while positive allosteric modulators of mGluR5 have not been tested in humans. Memantine has been proposed in early stages of schizophrenia, as it may counteract the effects of glutamate excitotoxicity correlated to high glutamate levels, slowing the progression of negative symptoms associated to more advanced stages of the illness
Policy choices and socioeconomic divides : long-term changes in Italy’s democratic quality
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Augmentation therapy of antipsychotics by no conventional drugs in schizophrenia treatment
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Italy’s majoritarian experiment : continuities and discontinuities in electoral behavior between the first and second republic
No full textDiffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Modelling depression in animals and the potential antidepressant effect of histaminergic modulation
No full textDepression is at the top position for "years lived with disability" (Smith, 2014). Its aetiology is unknown, but the pathogenesis implicates changes in glutamatergic neuronal plasticity. Glutamatergic plasticity likely mediates the effects of antidepressants acting through monoamines. Histamine is a monoaminergic neuromodulator able to regulate glutamatergic plasticity and synaptic transmission.The Flinders sensitive line (FSL) rat has face and predictive validity as model of depression when using traditional behavioural tests. However, these tests are usually missing complex explorative strategies that the animal performs in novel situations and that may be a relevant feature for a model of depression. We aimed to profile the FSL rat in terms of explorative strategies and coping styles displayed in a novel environment. The multivariate concentric square field™ (MCSF) consists of zones with different degrees of aversion. In the MCSF test, FSL rats showed lower exploratory drive, less recurrence to the shelter, and more risk assessment compared to Sprague Dawley rats, but no difference in risk-taking behaviours. In the novel cage test (consisting in a new bare environment) and in the home cage change test (to measure social behaviours), the FSL rat displayed a reactive coping style, described by immobility and lower aggression compared to Sprague Dawley rats. This profile shows similarities with temperaments and coping styles related to depression.Depression is linked to alteration of glutamatergic plasticity and similar alterations have been found in the hippocampus of FSL rats. Histamine H3 receptor (H3R) antagonists have displayed antidepressant properties in preclinical studies. We assessed the antidepressant properties of the H3R antagonist, clobenpropit, and its effect on hippocampal glutamatergic transmission in FSL rats. In the forced swim test, both systemic and hippocampal injections of clobenpropit reduced the immobility time. Clobenpropit improved memory in the novel object recognition and passive avoidance tests, with no effect on anxiety-related tests. Clobenpropit applied on hippocampal slices enhanced long-term synaptic potentiation (LTP), and, accordingly, in vivo administration increased the hippocampal levels of the NMDA receptor subunit GluN2A. Clobenpropit's effects both in the forced swim test and on LTP were prevented by blocking the hippocampal H1 and H2 receptors. In summary, clobenpropit exhibits antidepressant properties and regulates hippocampal glutamatergic plasticity, likely by an increase of histamine release and subsequent activation of the H1 and H2 receptors.Histamine receptors trigger intracellular signalling involved in the regulation of glutamatergic synaptic receptors, a mechanism that can affect synaptic strength. We assessed the histaminergic modulation of glutamatergic synaptic strength by recording miniature excitatory postsynaptic currents (mEPSCs) from CA1 pyramidal neurons in hippocampal slices from Sprague Dawley rats. The H1R, but not the H2R, agonist reduced mEPSC frequency, with no change of amplitude, suggesting a reduction of vesicle release probability. However, the paired-pulse facilitation (a measure of presynaptic release probability) was not altered by either the H1R or the H2R agonist, possibly due to a differential modulation of evoked versus spontaneous vesicle release. However, a postsynaptic origin of mEPSC frequency reduction cannot be excluded.List of scientific papersI. Magara S., Holst S., Lundberg S., Roman E., Lindskog M. Altered explorative strategies and reactive coping style in the FSL rat model of depression. Front Behav Neurosci. 21 April 2015. https://doi.org/10.3389/fnbeh.2015.00089 II. Femenia T., Magara S., DuPont C.M., Lindskog M. Hippocampal-dependent antidepressant action of the H3 receptor antagonist clobenpropit in a rat model of depression. Int J Neuropsychopharmacol. 2015. https://doi.org/10.1093/ijnp/pyv032 III. Magara S., Lindskog M. Histamine H1 and H2 receptor-mediated modulation of glutamatergic synaptic strength in the hippocampus. [Manuscript]</p
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