Efecto del envejecimiento sobre la organización y proliferación celular de la zona ventricular-subventgricular (V-SVZ) del cerebro del ratón

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2017/2018Introduction : Adult neurogenesis is the generation of new neurons from neural stem cells that, after maturing, integrate into pre - existing neural circuits. In the brain of mammals, two neurogenic niches have been identified: the ventricular - subventricular zone (V - SVZ) and the subgranular zone of the hippocampal dentate gyrus. The activity of these regions is finely regulated and is affected by various factors, such as aging, which affects their neurogenic capacity. Objective : Our aim was to prove if aging affects the structure and proliferative c apacity of the V - SVZ. Material and methods : We studied the V - SVZ of 2 - and 24 - month - old mice. The cellular organization of this region was compared by electron microscop y . Likewise, the presence of different cell types was studied by immunohistochemical de tection of specific molecular markers. Finally, the proliferative capacity of the V - SVZ was quantified in both experimental groups. Results: We observed that aging causes a slimming of the V - SVZ and other changes at the subcellular level, which are accompa nied by a decrease in the proliferative capacity of the region. Conclusion: Aging affects the proliferative capacity of V - SVZ. Further studies are required in order to ascertain the physiopathological implications of these changes in the brain.Introducción: La neurogénesis adulta consiste en la generación de n uevas neuronas a partir de células madre neurales que, tras madurar, se integran en circuitos preexistentes. En el cerebro de mamíferos se han identificado, principalmente, dos nichos neurogénicos: la zona ventricular - subventricular (V - SVZ) y la zona subgr anular del giro dentado del hipocampo. La actividad de estas r egiones está finamente regulada y se ve afectada por diversos factores, como el envejecimiento, que afectan a su capacidad neurogénica. Objetivo: Intentamos comprobar si el envejecimiento afecta a la estructura y capacidad proliferativa de la V - SVZ. Material y métodos: Estudiamos la V - SVZ de ratones de 2 y 24 meses de edad. Se comparó la organización celular de esta región mediante microscopía electrónica. Asimismo, se estudió la presencia de dis tintos tipos celulares mediante la detección inmunohistoquímica de marcadores moleculares específicos. Por otra parte, se cuantificó la capacidad proliferativa de la V - SVZ en ambos grupos experimentales. Resultados: Hemos observado que con el envejecimient o la V - SVZ sufre una reducción en su espesor y otros cambios a nivel subcelular, que van acompañados de una disminución en la capacidad proliferativa de la región. Conclusión: El envejecimiento afecta a la capacidad proliferativa de la V - SVZ. Se requieren nuevos trabajos que estudien las implicaciones fisiopatológicas de estos cambios en el cerebr

Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease

ObjectiveTo assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases.MethodA prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated.ResultsIn total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD.ConclusionPancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD