1,720,961 research outputs found
The role of CRF receptors in anxiety and depression: Implications of the novel CRF1 agonist cortagine
No full textCorticotropin-releasing factor (CRF), a 41 amino acid peptide exhibits its actions through two pharmacologically distinct CRF receptor subtypes CRF1 and CRF2. Regulation of the relative contribution of the two CRF receptors to central CRF activity may be essential in coordinating physiological responses to stress. To facilitate the analysis of their differential involvement, we recently developed a CRF1- selective agonist cortagine by synthesis of chimeric peptides derived from human/rat CRF, ovine CRF, and sauvagine. Cortagine was analyzed in behavioral experiments using male wild type and CRF2-deficient C57BL/6J mice for its action on anxiety- and depression-like behaviors. In contrast to the current hypothesis that increased CRF1 activity facilitates the expression of anxiety- and depression-like behavior, cortagine combines anxiogenic properties with antidepressant effects. In this article, we show that antidepressant effects are partially mediated by CRF1 of the dorsal hippocampus. Possible pathways responsible for the paradoxical antidepressant effects observed after CRF1 activation are discussed
Differential activation of CRF receptor subtypes removes stress-induced memory deficit and anxiety
No full textThe objective of this study was to investigate the role of corticotropin-releasing factor receptors 1 (CRF(1)) and 2 (CRF(2)) in anxiety-like behavior and learning of C57BL/6J mice after exposure to a stressful stimulus. When C57BL/6J mice were exposed to immobilization (1 h) serving as stressful stimulus, context- and tone-dependent fear conditioning were impaired if the training followed immediately after immobilization. The stress-induced impairment of context-dependent fear conditioning was prevented by specific blockade of CRF(2) of the lateral septum (LS) with anti-sauvagine-30. Immobilization did not only affect conditioned fear, but also enhanced, through CRF(2) of the LS, anxiety-like behavior determined with the elevated plus maze. Recovery from stress-induced anxiety and impairment of context-dependent fear conditioning was observed after 1 h delay of training and required hippocampal CRF(1), as indicated by the finding that this recovery was prevented by blockade of intrahippocampal CRF(1). It was concluded that exposure to a stressor initially affected both anxiety-like behavior and contextual conditioned fear through septal CRF(2), while the later activation of hippocampal CRF(1) resulted in the return to baseline levels of both processes. Intraventricular injection of mouse urocortin 2, a CRF(2)-selective agonist, removed the stress-induced anxiety and learning impairment, but did not reduce the activation of the hypothalamic pituitary adrenal axis indicative of the hormonal stress response. We propose that the enhanced anxiety is the component of the stress response responsible for the memory deficit
Cortagine, a specific agonist of corticotropin-releasing factor receptor subtype 1, is anxiogenic and antidepressive in the mouse model
No full textTwo subtypes of the corticotropin-releasing factor (CRF) receptor, CRF(1) and CRF(2), differentially modulate brain functions such as anxiety and memory. To facilitate the analysis of their differential involvement, we developed a CRF(1)-specific peptidic agonist by synthesis of chimeric peptides derived from human/rat CRF, ovine CRF (oCRF), and sauvagine (Svg). High affinity to the CRF-binding protein was prevented by introduction of glutamic acid in the binding site of the ligand. The resulting chimeric peptide, [Glu(21),Ala(40)][Svg(1-12)]x[human/rat CRF(14-30)]x[Svg(30-40)], named cortagine, was analyzed pharmacologically in cell culture by using human embryonic kidney-293 cells transfected with cDNA coding for CRF(1) or CRF(2), in autoradiographic experiments, and in behavior experiments using male C57BL/6J mice for its modulatory action on anxiety- and depression-like behaviors with the elevated plus-maze test and the forced swim test (FST), respectively. We observed that cortagine was more selective than oCRF, frequently used as CRF(1)-specific agonist, in stimulating the transfected cells to release cAMP. Cortagine's specificity was demonstrated in autoradiographic experiments by its selective binding to CRF(1) of brain sections of the mouse. After injection into the brain ventricles, it enhanced anxiety-like behavior on the elevated plus-maze at a lower dose than oCRF. Whereas at high doses, oCRF injected into the lateral intermediate septum containing predominantly CRF(2) increased anxiety-like behavior as CRF(2)-specific agonists do, cortagine did not. In contrast to its anxiogenic actions, cortagine reduced significantly the immobility time in the FST as described for antidepressive drugs. Thus, cortagine combines anxiogenic properties with antidepressive effects in the FST
Hippocampal c-Jun-N-Terminal Kinases Serve as Negative Regulators of Associative Learning
No full textIn the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 μm) ord-JNKI1 (8 μm) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 μg/μl), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin's ability to effectively inhibit protein synthesis as measured by c-Fos immunoreactivity. We also demonstrated milder and transient activation of the JNKs pathway in the CA1 subfield of the hippocampus during contextual fear conditioning and an enhancement of contextual fear after pharmacological inhibition of JNKs under baseline conditions. Finally, using combined biochemical and transgenic approaches with mutant mice lacking different members of the JNK family (Jnk1, Jnk2, andJnk3), we provided evidence that JNK2 and JNK3 are critically involved in stress-induced deficit of contextual fear, while JNK1 mainly regulates baseline learning in this behavioral task. Together, these results support the possibility that hippocampal JNKs serve as a critical molecular regulator in the formation of contextual fear.</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
The interaction between the anxiety and preconditioned fear - the roles of CRF receptors 1 and 2
No full textAppropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
