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Distribuição da proteína IMPACT em encéfalos de camundongos, ratos e sagüis / Distribution of the protein IMPACT in the mouse, marmoset brain

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Publico-11799m.pdf: 712324 bytes, checksum: 045cf67852c1de984973142eb424a0ec (MD5) / O controle da síntese protéica tem papel fundamental em diversas condições fisiológicas, mecanismos homeostáticos e diversos fenômenos de plasticidade neuronal. Um dos principais mecanismos de regulação da síntese protéica é a fosforilacão do fator de iniciação eIF2α. O aumento de fosforilação de eIF2α leva ao bloqueio do início de tradução geral da célula e tradução de genes específicos a exemplo do ATF4 (fator de ativação transcricional 4). Há 4 cinases específicas que fosforilam eIF2α, cada uma ativada sob condições distintas de estresse. A cinase GCN2, por exemplo, está presente em abundância no encéfalo, e faz parte do controle alimentar, memória e aprendizado de mamíferos. A proteína IMPACT, preferencialmente expressa no encéfalo, atua como uma inibidora da ativação de GCN2. Nesse contexto, torna-se relevante uma análise sistemática da distribuição de IMPACT no encéfalo e do possível envolvimento dessa proteína em condições fisiológicas e/ou patológicas. Um conjunto de resultados foi observado: (i) A proteína IMPACT é preferencialmente expressa em núcleos encefálicos associados ao ritmo circadiano, como também núcleos importantes na geração de ritmos, como o theta hipocampal; ii) A elevada intensidade e densidade de IMPACT no hipotálamo e hipocampo pode condizer com o envolvimento de IMPACT em mecanismos que envolvam homeostase corporal (função hipotalâmica) e memória (função hipocampal). (iii) Em tecido adulto, poucos grupos neuronais mostraram divergências na expressão de IMPACT entre roedores e primata; (iv) Há evidências de expressão diferencial (em uma mesma espécie) de IMPACT em grupos neuronais específicos (GABAérgicos); (v) Neurônios IMPACT-positivos são resistentes a vários tipos de estresse (leves, intensos, agudos ou crônicos, a exemplo de baixas temperaturas e indução de status epilepticus no modelo de epilepsia por pilocarpina); (vi) A proteína IMPACT é constitutiva, mostrou-se insensível a perturbações in vivo; (vii) IMPACT é detectada a partir do estágio embrionário E16. De acordo com os dados aqui dispostos sobre a expressão de IMPACT em neurônios e a evidência de sua expressão áreas encefálicas e em diversas condições, nós podemos especular sobre sua possível relevância na neurofisiologia. Assim, juntos esses dados sugerem que neurônios IMPACT-positivos tem função importante no encéfalo de mamíferos e podem estar envolvidos na geração e controle de ritmos encefálicos e na homeostase. / The control of protein synthesis plays a major role in several physiological conditions, homeostatic mechanisms and several phenomenon of neuronal plasticity. One of the most important mechanisms in regulation of protein synthesis is the phosphorylation of the initiation factor 2 (eIF2α). Increase in the eIF2α phosphorylation blocks general translation and enhance translation of specific genes such ATF4 (activating transcription factor 4) for example. In response to specific stress stimuli four specific kinases can phosphorylate eIF2α. The GCN2 kinase, for instance, is abundant in the brain, and is involved in feeding behavior control, learning and memory of mammalians. The IMPACT protein, preferentially expressed in the brain, acts as an inhibitor of the activation of GCN2. Therefore, a systematic analysis of the distribution of IMPACT in the brain and its possible involvement in physiological and/or pathological conditions are relevant. The following results were observed: (i) The IMPACT protein is preferentially expressed in brain nuclei involved in circadian rhythms, as well as in important nuclei involved in rhythm generation, such as the hippocampal theta rhythm; (ii) The high density and intensity of IMPACT labeling in the hypothalamus and hippocampus may reflect its involvement in homeostatic mechanisms (hypothalamic function) and memory (hippocampal function). (iii) In adult tissue, only a few neuronal groups showed divergence in IMPACT expression between rodents and primate; (iv) Within a single species there was differential expression of IMPACT in specific neuronal groups (e.g. GABAergic neurons); (v) IMPACT-positive neurons were resistant to several types of stress (weak, strong, acute or chronic), such as low temperature and status epilepticus induced by pilocarpine in a model of epilepsy; (vi) IMPACT is a constitutive protein, insensitive to perturbations in vivo; (vii) The detection of IMPACT starts at E16 embryonic stage. According to these results on the neurons expressing IMPACT and the evidence of its presence in some brain areas, we speculate on its possible relevance in neurophysiology. Thus, these data taken together suggest that IMPACT-positive neurons have important functions in the mammalian brains and may be involved in generation and control of brain rhythms and physiological homeostasis in general. / TEDE / BV UNIFESP: Teses e dissertações

Links & Downloads
  1. NEVES, Simone Ribeiro Bittencourt. Distribuição da proteína IMPACT em encéfalos de camundongos, ratos e sagüis. 2009. Tese (Doutorado) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.
  2. http://repositorio.unifesp.br/handle/11600/9337
  3. Publico-11799a.pdf
  4. Publico-11799b.pdf
  5. Publico-11799c.pdf
  6. Publico-11799d.pdf
  7. Publico-11799e.pdf
  8. Publico-11799f.pdf
  9. Publico-11799g.pdf
  10. Publico-11799h.pdf
  11. Publico-11799i.pdf
  12. Publico-11799j.pdf
  13. Publico-11799k.pdf
  14. Publico-11799l.pdf
  15. Publico-11799m.pdf
Tags
Embrião
Encéfalo
GCN1
GCN2
Hipocampo
Hipotálamo
Interneurônios
eIF2
Embryonic structures
Brain
Hippocampus
Hypothalamus
Interneurons
Additional Fields
Identiferoai:union.ndltd.org:IBICT/oai:repositorio.unifesp.br:11600/9337
Date26 November 2009
CreatorsBittencourt, Simone [UNIFESP]
ContributorsUniversidade Federal de São Paulo (UNIFESP), Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]
PublisherUniversidade Federal de São Paulo (UNIFESP)
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis
Format169 p.
Sourcereponame:Repositório Institucional da UNIFESP, instname:Universidade Federal de São Paulo, instacron:UNIFESP
Rightsinfo:eu-repo/semantics/openAccess

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