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Doctoral Thesis
DOI
10.11606/T.87.2008.tde-10032009-113854
Document
Author
Full name
Camila Teixeira Mendes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Dias Neto, Emmanuel (President)
Camargo, Anamaria Aranha
Carramaschi, Lygia da Veiga Pereira
Haddad, Luciana Amaral
Moreira, Eloisa de Sá
Title in Portuguese
Lítio e expressão gênica: implicações para a doença de Alzheimer.
Keywords in Portuguese
Doença de Alzheimer
Expressão gênica
GSK3b
Lítio
Proteoma
RASH
Abstract in Portuguese
A expressão aumentada de GSK3b em pacientes da doença de Alzheimer (DA), aparentemente está relacionada com a formação de placas senis e emaranhados neurofibrilares. Utilizamos qPCR para avaliar os efeitos do lítio sobre os níveis do mRNA de GSK3a e GSK3b em culturas primárias de neurônios corticais e hipocampais de rato tratados com lítio. Nossos resultados, sugeriram que lítio é capaz de reduzir os níveis de mRNA de Gsk3b hipocampal de modo específico e dose-dependente. Estes dados foram subsequentemente comprovados in vivo em amostras cerebrais de ratos tratados com LiCl. Utilizamos hibridização subtrativa de cDNA e eletroforese bidimensional de culturas de neurônios hipocampais tratados com o lítio. Nossos estudos sugeriram a expressão diferencial de 88 genes, além de oito proteínas com cerca de 50% de alteração de expressão. Estas observações sugerem novos efeitos regulatórios do lítio sobre GSK3b e fornecem potenciais alvos da ação do lítio.
Title in English
Lithium and gene expression: implications to Alzheimer disease.
Keywords in English
Alzheimer
Gene expression
GSK3b
Lithium
Proteoma
RASH
Abstract in English
The increased systemic expression of active GSK3b in Alzheimers disease (AD) patients apparently is associated with the formation of senile plaques and neurofibrillary tangles, the hallmarks of this disease. In this study we used qPCR to evaluate the transcriptional regulation of GSK3a and GSK3b in lithium-treated primary cultures of rat cortical and hippocampal neurons. We found a significant and dose-dependent reduction in the mRNA levels of GSK3b, which was specific to hippocampus. This same effect was further confirmed in vivo by measuring GSK3 expression in different brain regions of adult rats treated with lithium. We used subtractive hybridizations and two-dimensional electrophoresis patterns of culture of hippocampus neurons treated with lithium. Our study suggested 88 genes differently expressed besides 8 proteins identified with variation expression. These observations suggest new regulatory effects of lithium over GSK3b and suggesting new potential lithium action targets.
 
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Publishing Date
2009-03-19
 
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