Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. In the present study adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD) for 4 weeks. Measurements by in situ hybridization and Western blotting showed that CSD significantly increased mRNA and protein levels of the norepinephrine transporter (NET) in the LC region and NET protein levels in the hippocampus, frontal cortex and amygdala. CSD-induced increases in NET expression were abolished by adrenalectomy or treatment with corticosteroid receptor antagonists, suggesting the involvement of corticosterone and corticosteroid receptors in this upregulation. Furthermore, protein levels of protein kinase A (PKA), protein kinase C (PKC), and phosphorylated cAMP-response element binding (pCREB) protein were significantly reduced in the LC and its terminal regions by the CSD paradigm. Similarly, these reduced protein levels caused by CSD were prevented by adrenalectomy. However, effects of corticosteroid receptor antagonists on CSD-induced down-regulation of PKA, PKC, and pCREB proteins were not consistent. While mifeprestone and spironolactone, either alone or in combination, totally abrogate CSD effects on these protein levels of PKA, PKC and pCREB in the LC and those in the hippocampus, frontal cortex and amygdala, their effects on PKA and PKC in the hippocampus, frontal cortex and amygdala were region-dependent. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression.

Our previous studies demonstrated that chronic social defeat (CSD) up-regulated expression of the serotonin transporter (SERT) and norepinephrine transporter (NET) in the brain, which was mediated by corticosteroid receptors. In the present study we first analyzed the alterations of corticosteroid receptors in different brain regions after the CSD paradigm. The results showed that CSD significantly reduced glucocorticoid receptor (GR) protein levels in the CA1 and dentate gyrus of the hippocampus, as well as in central and basolateral nuclei of the amygdala, which was accompanied by the translocation of GR from cytoplasm to nuclei. CSD also markedly reduced GR mRNA levels and MR immunoreactivity in the CA1, CA3 and dentate gyrus areas of the hippocampus. Conversely, CSD pronouncedly enhanced GR mRNA and protein levels in the dorsal raphe nucleus and locus coeruleus relative to the control. As an extension of our previous studies, in situ hybridization and immunohistochemical staining demonstrated that CSD regimen caused a notable increase of SERT mRNA levels in the dorsal raphe nucleus and increased SERT immunoreactivities in CA1 and CA3 of the hippocampus, as well as those in the basolateral nuclei of the amygdala. Likewise, CSD regimen resulted in an evident enhancement of NET immunoreactivity in the CA1 of the hippocampus and in the basolateral nuclei of the amygdala. Our current findings suggest that GR expressional alterations in response to CSD are complex and brain region-specific, which may correspond to their different functions in these regions.

No description available.

No description available.

Transtornos depressivos afetam de 1-6% dos adolescentes a cada ano ao redor do mundo. Esse aparecimento precoce anuncia uma doença mais grave e persistente na vida adulta, sendo considerada a terceira principal causa de suicídio na faixa etária entre 14-29 anos. Os exatos mecanismos moleculares envolvidos na fisiopatologia da depressão ainda não são compreendidos, e muitos estudos destacam o processo de apoptose como um possível mecanismo de contribuição para a depressão relacionada ao estresse crônico. Desta forma, o objetivo deste trabalho foi avaliar os efeitos da submissão social em camundongos machos adolescentes, sobre comportamentos emocionais e sobre a localização celular hipocampal do fator de transcrição Max. Metodologia: Camundongos machos adolescentes, C57BL/6, foram submetidos durante 21 dias consecutivos a um modelo de submissão social e ambos os grupos, experimental (n=16) e controle (n=16) foram analisados nos aspectos comportamental, expressão gênica e localização da proteína Max. Resultados: Dados retidos devido à solicitação (publicação de dados, patentes ou diretos autorais). / Depressive disorders affect 1-6% of adolescents each year around the world. This early appearance heralds a more serious and persistent disease in adulthood, being considered the third leading cause of suicide in people aged between 14-29 years. The precise molecular mechanisms involved in the pathophysiology of depression are not yet understood, and many studies highlight the process of apoptosis as a possible mechanism contributing to depression related to chronic stress. Thus, the objective of this study was to evaluate the effects of social defeat in male adolescent mice on emotional behavior and on hippocampal cellular setting of the Max transcription factor. Methodology: C57BL/6 male mice were submitted to 21 consecutive days of a model for social defeat and, both the experimental (n=16) and control groups (n=16) were investigated for behavioral analysis and also for the Max protein expression and settings. Results: Request to retain data (publication, patent or copyright directs).

Relações entre machos de roedores muitas vezes se dão com a manifestação de comportamentos agressivos, em um embate em que se define um perdedor e um ganhador. O macho perdedor, de acordo com experimentos realizados no laboratório, apresenta comportamentos de defesa (avaliação de risco) quando exposto ao contexto da derrota social. Na expressão da defesa condicionada, estruturas do hipotálamo lateral devem ser importantes, que são também mobilizadas durante o confronto. No hipotálamo lateral destacamos a a parte justadorsomedial do hipotálamo lateral (LHAjd) que tem conexões com o sistema septo-hipocampal e projeta-se liga ao prémamilar dorsal (PMD), crítico para a expressão de comportamentos de defesa. Por outro lado, o PMD, que é uma estrutura altamente mobilizada durante o confronto social, tem conexões com o núcleo anteromedial do tálamo (AMv), estrutura já conhecida pela sua importância na aquisição da memória contextual e espacial. Assim, no presente trabalho, investigamos o papel do LHAjd na expressão e do AMv na aquisição da defesa condicionada na derrota social. Nos animais com lesão do LHAjd, observamos diminuição nos comportamentos de avaliação de risco durante exposição ao contexto. Nos animais com lesão do AMv o mesmo efeito. Dado os efeitos das lesões no AMv, elaboramos um paradigma para estudo em camundongos, a fim de se realizar inativações pontuais com farmacogenética nos neurônios glutamatérgicos em animais transgênicos durante a derrota social. Foi observado o mesmo padrão em camundongos transgênicos vGlut2-cre inativados com farmacogenética, não havendo influência nos comportamentos durante a derrota social. Inativações antes do contexto não causaram efeito na defesa condicionada. As inativações durante a derrota, no entanto, não tiveram efeito quando o residente agressivo está na exposição ao contexto. Os dados sugerem que o LHAjd tem papel na expressão da defesa condicionada, enquanto que o AMv tem papel na aquisição da defesa condicionada ao contexto, mas não no reconhecimento do residente agressivo. / Male rodents may interact aggressively, and from the agonistic encounter, it results a winner and a defeated animal. Accordingingly, the defeated male shows defensive behaviors (risk assessment) to the social defeat-related context. Contextual responses are known to rely on hippocampal processing, and one of the main targets of the hippocampal system is the justodorsomedial part of lateral hypothalamus (LHAjd), which projects to dorsal premamillary nucleus (PMD), known to be involved in the expression of social defensive behaviors. Notably, PMD, a hypothalamic site highly responsive to the social defeat, in turn, projects to the ventral part of thalamic anteromedial nucleus (AMv), previously shown to be involved in the acquistion of spatial and contextual memory to predatory threats. Thus, in present study, we investigated the role of LHAjd in expression and of AMv in acquisition of social defeat conditioned defensive behaviors. In LHAjd lesioned animals, we observed a decrease in risk assessment behaviors during exposute to the social defeat associated context , but not during the social defeat itself, suggesting a role in the expression of contextual but not in the innate social defeat. In AMv lesioned animals, we observed that the animals lost contextual defensive response, suggesting a role in the acquisition and/or expression of contextual responses. Next, using pharmacogetic inhibition, we investigated in vGlut2-cre transgenic mice the role of the AMV in the acquisition and expression of contextual defensive behavior. We have found that AMV inactivation prior to the social defeaf, but not prior to the exposure to the social defeat related context, was able to decrease contextual responses in animals tested withot the presence of the male aggressor, but not in the situation where the male aggressor was present. Overall, our results suggest that the LHAjd has a role in the expression of conditioned defense, and that the AMV is involved in the acquisision of contextual fear responses, but not in social recognition of aggressive male.

Notre travail se propose d’analyser selon quelles modalités se mettent en place et évoluent les intégrations élitaires de type thermidorien qui sont à l’oeuvre au Cameroun de 1992 à 2011, au travers des transactions liées à la candidature aux élections présidentielles.En décembre 1990, après 4 décennies d’un régime présidentiel monolithique, des forces d’opposition émergent à l’occasion de la libéralisation de la vie politique, dans l’optique de renverser le pouvoir en place, dans une logique révolutionnaire. Au bout de deux décennies de pluralisme, à défaut d’avoir remplacé le pouvoir en place, certains des membres de la fronde contre le pouvoir sont intégrés dans les instances gouvernementales du régime, occasionnant une révolution thermidorienne. Nous passons en revue les différents éléments (systémiques et conjoncturels) facilitateurs de l’intégration élitaire, au sortir d’une période autoritaire et qui favorisent les intégrations des anciens révolutionnaires dans le centre du pouvoir. Les conditions analysées sont les suivantes en ce qui concerne les éléments systémiques : une structuration élitaire centralisée qui freine la mise en place d’un polycentre, une opposition autonome, un recrutement élitaire décentralisé, le mésocratisme comme coutume du champ politique. Les éléments conjoncturels qui initient l’intégration élitaire postautoritaire, et que nous analysons, sont les suivants : la possession par les élites émergeantes des caractéristiques de la nouvelle donne du jeu politique (référentiels démocratiques), le défaut de cette nouvelle caractéristique chez les élites en position dans le pouvoir central, la capacité chez les élites intermédiaires d’exercer une pression sur le centre du pouvoir, afin de modifier l’agenda politique, et enfin, la possibilité pour les élites en place de mettre à profit les leviers institutionnels dont ils disposent pour rassembler les différentes factions en présence / Our work aims at studying how the thermidorian-type elite integrations witnessed in Cameroon from 1992 to 2011 are set up and evolve, based on transactions linked to the candidacy for presidential elections. In december 1990, after 4 decades of one-party presidential system, opposition forces emerged thanks to the liberalisation of political life in december 1990, with the aim of toppling the powers that be, through a revolutionary move. After two decades of pluralism, some members of the opposition who have not succeeded to replace the people in power are integrated into public bodies of the regime, thus causing a thermidorian revolution. We are reviewing the various elements (system andsituational) facilitating elite integration at the end of an authoritarian period and which foster the integration of former revolutionaries into the centre of power. The following conditions are reviewed, including: a centralised elite structure which hinders the setting up of a polycentre for an independent opposition, a decentralised elite recruitment, mesocratism as a practice in the political field. Situational elements which promote the integration of post-authoritarian elite and that we are analysing are the following :emerging elite possess the characteristics of the new order of political game (democraticreferences), elite in the central power lack of this new characteristics, intermediary elite are able to mount pressure on the central power to change the political agenda, and lastly, the elite in power can use institutional levers at their disposal to bring the various existing factions together

No description available.

<p>Ceramics constitute an important group of low-density armour materials. Their high intrinsic strength makes it possible to design ceramic armour systems capable of defeating projectiles directly on the ceramic surface. This capability, named interface defeat, signifies that the projectile material is forced to flow radially outwards on the surface of the ceramic without penetrating significantly.</p><p>This thesis presents impact experiments between long-rod projectiles and ceramic targets. The projectile/target interaction was studied using flash X-ray technique. Transition velocities (the impact velocity at which interface defeat can no longer be maintained and penetration starts) were estimated for different combinations of metallic projectiles and ceramic targets and compared to critical velocities estimated on a theoretical basis. Replica scaling experiments were also performed in order to investigate the possible influence of scale.</p><p>All ceramic materials tested showed a distinct transition from interface defeat to penetration. Experiments with different silicon carbides showed that the transition velocity correlated better with the fracture toughness than with the hardness of the ceramic materials. For conical projectiles, penetration occurred along a conical surface crack and at a lower transition velocity than that observed for cylindrical projectiles. Experiments with unconfined alumina targets in different scales showed only a slight increase in dimensionless final penetration with length scale.</p><p>A unique transition velocity seems to exist for each combination of projectile, target material and target configuration. This velocity was found to depend on both the strength (hardness) and the brittleness (fracture toughness) of the ceramic. The lower transition velocity of conical projectiles compared with cylindrical ones is mainly due to the radially expanding load and the penetration of projectile material into surface cracks. The results of the experiments in different scales indicate that replica scaling is valid for penetration in ceramics.</p>

Ceramics constitute an important group of low-density armour materials. Their high intrinsic strength makes it possible to design ceramic armour systems capable of defeating projectiles directly on the ceramic surface. This capability, named interface defeat, signifies that the projectile material is forced to flow radially outwards on the surface of the ceramic without penetrating significantly. This thesis presents impact experiments between long-rod projectiles and ceramic targets. The projectile/target interaction was studied using flash X-ray technique. Transition velocities (the impact velocity at which interface defeat can no longer be maintained and penetration starts) were estimated for different combinations of metallic projectiles and ceramic targets and compared to critical velocities estimated on a theoretical basis. Replica scaling experiments were also performed in order to investigate the possible influence of scale. All ceramic materials tested showed a distinct transition from interface defeat to penetration. Experiments with different silicon carbides showed that the transition velocity correlated better with the fracture toughness than with the hardness of the ceramic materials. For conical projectiles, penetration occurred along a conical surface crack and at a lower transition velocity than that observed for cylindrical projectiles. Experiments with unconfined alumina targets in different scales showed only a slight increase in dimensionless final penetration with length scale. A unique transition velocity seems to exist for each combination of projectile, target material and target configuration. This velocity was found to depend on both the strength (hardness) and the brittleness (fracture toughness) of the ceramic. The lower transition velocity of conical projectiles compared with cylindrical ones is mainly due to the radially expanding load and the penetration of projectile material into surface cracks. The results of the experiments in different scales indicate that replica scaling is valid for penetration in ceramics.