1,720,986 research outputs found
Melatonin and its new agonist S-20098 restore synchronized sleep fragmented by experimental trypanosome infection in the rat
The experimental infection with the parasite Trypanosoma brucei in the rat provides a unique model of dysfunction of the sleep regulatory mechanisms, because the length of synchronized sleep episodes is selectively and dramatically reduced in the advanced stages of the disease. In the present study, melatonin was acutely administered (3 mg/kg SC) to trypanosome-infected rats, before the sleep onset. This treatment resulted in a significant increase of the length of synchronized sleep episodes in respect to the infected animals and to those that had received only the vehicle. Thus, melatonin restored a normal sleep pattern during the infection. Similar findings were obtained with the new melatonin agonist S-20098. The sleep parameters were not significantly modified by either melatonin or S-20098 acute administration to noninfected animals. These findings indicate that exogenous melatonin and S-20098 exert a selective regulatory action on sleep fragmentation during experimental trypanosomiasis
Modulation of Arc and BDNF following acute and chronic administration of agomelatine in rats
Synergic mechanisms in the modulation of BDNF and Arc following agomelatine administration
Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine
Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration
Objectives. The aim of this study was to investigate the acute modulation of the neurotrophin Brain-derived neurotrophic factor (BDNF) by the novel antidepressant agomelatine and the relative contribution of its melatonergic and serotonergic receptor components. Methods. BDNF mRNA levels were measured in rat hippocampus and prefrontal cortex after acute administration of agomelatine, melatonin or the 5-HT2C antagonist S32006. Results. BDNF expression was significantly increased 16 h after acute agomelatine administration, an effect that follows a specific temporal profile, is limited to the prefrontal cortex and it is due to changes of specific neurotrophin transcripts. Moreover, the acute up-regulation of BDNF mRNA levels appears to be the result of a synergistic effect between the melatonergic properties of agomelatine as MT1/MT2 agonist and its serotonergic 5-HT2C antagonism, since either melatonin or the 5-HT2C antagonist S32006 does not mimic the effects of agomelatine. Conclusions. These data provide evidence that acute agomelatine treatment modulates the expression of BDNF through a functional interaction between melatonergic MT1/MT2 and serotonergic 5-HT2C receptors, supporting the notion that intracellular events can be regulated via a synergistic activity of different neuromodulatory system
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Transcriptional changes of BDNF and clock genes in the rat prefrontal cortex following acute agomelatine administration
Purpose: Depression is a complex disorder characterized by an array of changes affecting neurotransmitters, hormones as well as proteins important for neuronal resilience. While synaptic events represent the first step in the action of antidepressant drugs, the investigation of downstream changes involving signalling and transcriptional mechanisms allow the characterization of targets that may contribute to functional changes in selected brain regions with relevant implications for the clinical outcome. Agomelatine is a new antidepressant with melatonergic MT1/2 receptor agonist and 5-HT2C receptor antagonist properties with antidepressant activity in preclinical models as well as in Major Depressive Disorders [1]. The aim of this study was to investigate the time course of changes produced by acute treatment with agomelatine on the expression of the neurotrophin Brain-Derived Neurotrophic Factor (BDNF), as well as the relative contribution of melatonergic and 5-HT2C receptors in the actions of agomelatine. Moreover, we investigated if the potential BDNF mRNA changes induced by agomelatine could result, at least in part, from alterations on different clock genes (PER 1 and 2, CRY 1 and 2, CLOCK) expression.
Methods: Male Sprague-Dawley rats were given a single in- jection of agomelatine (40mg/kg i.p.) or vehicle and BDNF mRNA expression was analyzed 1, 7 or 16h after. To evaluate the contribution of MT1/2 and 5HT2C receptors, rats were acutely treated with melatonin (40mg/kg i.p.), the 5HT2C antagonist S32006 (10 mg/kg i.p.) or the MT1/2 antagonist S22153 (20 mg/kg i.p.) in the presence of agomelatine or vehicle and killed 16 h after. PER 1 and 2, CRY 1 and 2 and CLOCK mRNA expression was assessed 7 and 16 h after agomelatine and vehicle treatment.
Results: BDNF expression was significantly increased 16h after acute agomelatine administration, an effect that follows a specific temporal profile, is limited to the prefrontal cortex and it is due to changes of specific neurotrophin transcripts, including exon I, III and IV. Moreover, the acute up-regulation of BDNF mRNA levels appears to be the result of a synergistic effect between the melatonergic properties of agomelatine as MT1/MT2 agonist and its serotonergic 5-HT2C antagonism, since either melatonin or the 5-HT2C antagonist S32006 does not mimic the effects of agomelatine and pretreatment with the MT1/2 antagonist S22153 prevented the BDNF up regulation induced by agomelatine. We also found that acute agomelatine produced a significant increase of some clock genes in the rat prefrontal cortex, including PER 1, CRY 1 and CRY 2. Interestingly, most of these changes were anticipated with respect to what observed for BDNF, since they were evident at 7 h post treatment.
Conclusions: Taken together, these data provide evidence that acute agomelatine treatment modulates the expression of BDNF in the rat prefrontal cortex through a functional interaction between melatonergic MT1/MT2 and 5-HT2C receptors. Since such effect appears to originate from changes in the circadian variation of BDNF expression, we suggest that agomelatine may exert at least part of its modulatory activity through the rapid regulation of several clock genes.
References
[1] Goodwin, G.M., Emsley R, Rembry S, Rouillon F (2009) Agomelatine prevents relapse in patients with major depressive disorder without ev- idence of a discontinuation syndrome: a 24-week randomized, double- blind, placebo-controlled trial. J Clin Psychiatry, 70:8, 1128−37
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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