IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Oxidative distress in Alzheimer Disease human organoids
Autor/es:
HOLUBIEC, MARIANA INÉS
Reunión:
Congreso; XXXV Annual Meeting of the Argentinian Society for Neuroscience Research; 2020
Resumen:
While highly polarized neurons deal with physiological changes in local levels of reactive oxygenspecies (ROS), it is known that in early stages of Alzheimer disease (AD) imbalances in themanagement of ROS occur, promoting abnormal macromolecules oxidation. To test the association of increased oxidation and intracellular dynamic defects in the progression of AD we developed human brain organoids from iPSC control and APP Swedish mutation (APPSwe). We characterized organoid cell composition and AD pathological hallmarks, such as amyloid-like deposits stained with antibodies and classical Congo-red. Furthermore, we observed, in APPSwe organoids, an increase in Aβ reactivearea as well as a decrease in full length APP levels by western blot and immunostaining. In addition, we developed a technique for microinjecting organoids with viral vectors or probes to measure mitochondrial dynamics and morphology, superoxide anion levels and reactive oxygen species. We found a significant increase of superoxide anion levels in live imaging of APPSwe organoids. We also described an increase in Glutaredoxin-2 reactive area and integrated intensity, suggesting changes in thiol-based regulation in AD. Our results highlight the relevance of modeling neurological diseases using complex tissue arrangements, and points to a clear impairment in oxidative stress pathways that, if modulated, could be used as a therapeutic strategy for treatment of abnormal oxidation in AD.