Estudio de la contribución de la exposición a polución ambiental del aire urbano de Santiago en la inducción del fenotipo clínico de la demencia frontotemporal en el modelo Murino C9ORF72
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Fecha
2021
Profesor/a Guía
Facultad/escuela
Idioma
es
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Universidad Andrés Bello
Nombre de Curso
Licencia CC
Licencia CC
Resumen
La polución ambiental del aire es una mezcla compleja de gases y nanopartículas
(NPs) que se encuentran dispersas ampliamente en el ambiente y que pueden
tener efectos tóxicos en la salud humana. Las NPs ingresan al organismo,
difundiendo hacia diferentes tejidos incluyendo el sistema nervioso central. En la
actualidad este estresor ambiental es una problemática mundial y el área
metropolitana de Santiago (AMS) de Chile no es la excepción. La exposición
crónica a PM2,5 y NPs de la polución ambiental urbana ha documentado tener
efectos negativos para quienes padecen de la enfermedad de Alzheimer (EA) y
si además hay presencia de un factor de riesgo genético, se acelera la aparición
de la enfermedad. La demencia frontotemporal (DFT) es un espectro
neurodegenerativo de múltiples fenotipos clínicos y la mutante C9ORF72 es
factor de riesgo genético. A diferencia de la EA, no existe evidencia que relacione
la DFT y la polución ambiental del aire. Es por eso que nos preguntamos ¿es
posible que las NPs provenientes de la polución ambiental del aire contribuyan al
desarrollo del deterioro cognitivo y neuroinflamación asociados a la patogénesis
de DFT, tal como sucede en la EA? Para resolver esta pregunta se planteó que
“la exposición de un modelo murino de DFT a las NPs provenientes de la polución
ambiental del aire del área metropolitana de Santiago de Chile provoca trastornos
cognitivos, motores y psicológicos e induce inflamación mediada por glías
activadas”. Para poner a prueba nuestra hipótesis utilizamos el modelo murino
transgénico C9ORF72, caracterizado por no presentar deficiencia cognitiva (test
de NOR) en su edad adulta ni activación glial. Los animales fueron expuestos a
la polución ambiental urbana del AMS, donde se evaluó mediante una batería de
pruebas conductuales, si dicho estresor ambiental, indujo alguno de los
trastornos planteados y además mediante inmunofluorescencia, si indujo la
presencia de marcadores de activación glial. La exposición a polución ambiental
urbana resulto en: declive cognitivo, trastornos psicológicos, pero no problemas
motores, en conjunto con astrogliosis hipocampal en CA1. Estos datos sugieren
que las NPs de la polución ambiental del aire podrían contribuir al desarrollo de
la patogénesis de DFT en el modelo C9ORF72.
Air pollution is a complex mixture of gases and nanoparticles (NPs) that are widely dispersed in the environment and have been described to have detrimental effects in human health. NPs enter the body, and spread to several tissues, including the central nervous system. This environmental stressor has become a global trend and the metropolitan area of Santiago, Chile is not an exception. Chronic exposure to PM2,5 and NPs from urban air pollution have been documented to have negative effects for those suffering Alzheimer’s disease (AD), and the evidence suggests that the presence of a genetic risk factor for AD accelerates the appearance of the disease. Frontotemporal dementia (FTD) is a neurodegenerative spectrum of diverse clinical phenotypes, in which the mutant C9ORF72 is a genetic risk factor. Unlike AD, the evidence associating exposure to urban air pollution and FTD has not been studied yet. Is it possible that urban air pollution’s NPs induce the development of cognitive impairment and neuroinflammation associated with the pathogenesis of FTD, as in AD? our hypothesis was that “the exposure of a murine model of FTD to the NPs from the urban air pollution of metropolitan Santiago area induces cognitive, psychological and motor deficits, as well as glial activation mediated-inflammation”. To test this, we used the transgenic murine model C9ORF72, which has been previously reported not to present cognitive deficits (in the NOR test) or astrogliosis in adult mice. C9orf72 mice were exposed to the urban air pollution of Santiago. Several behavioral tests were performed to determine whether this environmental stressor triggers cognitive, motors and psychological impairments, and by immunofluorescence, whether it induces glial activation-mediated inflammation. In this thesis we observed cognitive decline, psychological alterations and hippocampal astrogliosis in CA1. In consequence, we conclude that exposure of urban air pollution triggers the development of FTD in the C9ORF72 transgenic mouse model.
Air pollution is a complex mixture of gases and nanoparticles (NPs) that are widely dispersed in the environment and have been described to have detrimental effects in human health. NPs enter the body, and spread to several tissues, including the central nervous system. This environmental stressor has become a global trend and the metropolitan area of Santiago, Chile is not an exception. Chronic exposure to PM2,5 and NPs from urban air pollution have been documented to have negative effects for those suffering Alzheimer’s disease (AD), and the evidence suggests that the presence of a genetic risk factor for AD accelerates the appearance of the disease. Frontotemporal dementia (FTD) is a neurodegenerative spectrum of diverse clinical phenotypes, in which the mutant C9ORF72 is a genetic risk factor. Unlike AD, the evidence associating exposure to urban air pollution and FTD has not been studied yet. Is it possible that urban air pollution’s NPs induce the development of cognitive impairment and neuroinflammation associated with the pathogenesis of FTD, as in AD? our hypothesis was that “the exposure of a murine model of FTD to the NPs from the urban air pollution of metropolitan Santiago area induces cognitive, psychological and motor deficits, as well as glial activation mediated-inflammation”. To test this, we used the transgenic murine model C9ORF72, which has been previously reported not to present cognitive deficits (in the NOR test) or astrogliosis in adult mice. C9orf72 mice were exposed to the urban air pollution of Santiago. Several behavioral tests were performed to determine whether this environmental stressor triggers cognitive, motors and psychological impairments, and by immunofluorescence, whether it induces glial activation-mediated inflammation. In this thesis we observed cognitive decline, psychological alterations and hippocampal astrogliosis in CA1. In consequence, we conclude that exposure of urban air pollution triggers the development of FTD in the C9ORF72 transgenic mouse model.
Notas
Tesis (Licenciado en Biología)
Palabras clave
Contaminación Ambiental, Demencia Frontotemporal, Aspectos Ambientales, Chile, Santiago