RESUMEN
Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies.
Asunto(s)
Bioensayo/métodos , Yema de Huevo/metabolismo , Metabolismo de los Lípidos , Pez Cebra/embriología , Pez Cebra/metabolismo , Absorción Fisiológica/efectos de los fármacos , Animales , Transporte Biológico/efectos de los fármacos , Compuestos de Boro/metabolismo , Yema de Huevo/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Ácidos Grasos/metabolismo , Humanos , Larva/efectos de los fármacos , Larva/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Reproducibilidad de los Resultados , Coloración y Etiquetado , Factores de Tiempo , Proteínas de Pez Cebra/metabolismoRESUMEN
Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia.
Asunto(s)
Enfermedad de Alzheimer/patología , Antígeno CTLA-4/metabolismo , Demencia Frontotemporal/patología , Linfocitos T/metabolismo , Antígenos CD/metabolismo , Linfocitos B/metabolismo , Brasil , Femenino , Antígenos HLA-DR/metabolismo , Humanos , MasculinoRESUMEN
BACKGROUND: Genetic variation plays an important role in Bipolar Disorder (BD) and suicide susceptibility. However, little is known about the genetic influence on the risk of suicide, particularly in BD patients. Since FOXO3A plays a role in distinct mood-relevant behavioral processes, this gene could be a novel gene candidate for BD. Thus, we investigated whether FOXO3A polymorphisms are associated with BD and suicidal behavior in BD patients. METHODS: TaqMan genotyping was used to detect FOXO3A SNPs in 273 BD patients and 264 control subjects. RESULTS: Three SNPs (rs1536057, rs2802292 and rs1935952) were associated with BD, but none was positively linked with suicidal behavior. LIMITATION: A systematic evaluation within the whole FOXO3A gene and drug treatment in patients was not performed. CONCLUSIONS: These data suggest that FOXO3A is a novel susceptibility locus for BD, but not for suicidal behavior in BD patients. These results may contribute to a better understanding of the BD genetics.