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1.
Hippocampus ; 27(1): 36-51, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27701786

RESUMO

It is well known that adult neurogenesis occurs in two distinct regions, the subgranular zone of the dentate gyrus and the subventricular zone along the walls of the lateral ventricles. Until now, the contribution of these newly born neurons to behavior and cognition is still uncertain. The current study tested the functional impacts of diminished hippocampal neurogenesis on emotional and cognitive functions in transgenic Gfap-tk mice. Our results showed that anxiety-related behavior evaluated both in the elevated plus maze as well as in the open field, social interaction in the sociability test, and spatial working memory in the spontaneous alternation test were not affected. On the other hand, recognition and emotional memory in the object recognition test and contextual fear conditioning, and hippocampal long-term potentiation were impaired in transgenic mice. Furthermore, we evaluated whether environmental enrichment together with physical exercise could improve or even restore the level of adult neurogenesis, as well as the behavioral functions. Our results clearly demonstrated that environmental enrichment together with physical exercise successfully elevated the overall number of progenitor cells and young neurons in the dentate gyrus of transgenic mice. Furthermore, it led to a significant improvement in object recognition memory and contextual fear conditioning, and reverted impairments in hippocampal long-term potentiation. Thus, our results confirm the importance of adult neurogenesis for learning and memory processes and for hippocampal circuitry in general. Environmental enrichment and physical exercise beneficially influenced adult neurogenesis after it had been disrupted and most importantly recovered cognitive functions and long-term potentiation. © 2016 Wiley Periodicals, Inc.


Assuntos
Transtornos Cognitivos/terapia , Meio Ambiente , Hipocampo/fisiopatologia , Potenciação de Longa Duração/fisiologia , Atividade Motora/fisiologia , Neurogênese/fisiologia , Animais , Ansiedade/patologia , Ansiedade/fisiopatologia , Ansiedade/terapia , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Condicionamento Psicológico/fisiologia , Modelos Animais de Doenças , Terapia por Exercício , Medo/fisiologia , Hipocampo/patologia , Abrigo para Animais , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/patologia , Neurônios/fisiologia , Reconhecimento Psicológico/fisiologia , Comportamento Social
2.
BMC Genomics ; 13: 141, 2012 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-22524407

RESUMO

BACKGROUND: Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. RESULTS: The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. CONCLUSIONS: The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized pathogen. Plasmid pJA144188 revealed a modular architecture of gene regions that contribute to the multi-drug resistance of C. resistens DSM 45100. The tet(W) gene encoding a ribosomal protection protein is reported here for the first time in corynebacteria. Cloning of the tet(W) gene mediated resistance to second generation tetracyclines in C. glutamicum, indicating that it might be responsible for the failure of minocycline therapies in patients with C. resistens bacteremia.


Assuntos
Corynebacterium/efeitos dos fármacos , Corynebacterium/genética , Resistência a Múltiplos Medicamentos/genética , Genoma Bacteriano , Aminoácidos/metabolismo , Proteínas de Bactérias/genética , Cromossomos Bacterianos , Corynebacterium/metabolismo , Ordem dos Genes , Histidina/metabolismo , Humanos , Leucemia Mieloide Aguda/microbiologia , Redes e Vias Metabólicas , Testes de Sensibilidade Microbiana , Anotação de Sequência Molecular , Dados de Sequência Molecular , Proteínas de Ligação às Penicilinas/genética , Plasmídeos/genética , Análise de Sequência de DNA , Fatores de Virulência/genética
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