Seminario de la Dra. Rommy Von Bernhardi M.

seminario iibce

El próximo Seminario IIBCE será el miércoles 3/4 a las 11:30 h en el salón de actos del Instituto (Av Italia 3318).

Presentará Rommy Von Bernhardi Montgomery, Department of Neurology, Pontificia Universidad Catolica School  of Medicine. Santiago, Chile:

 

Age-dependent dysregulation of microglial cell activation

Resumen:
Aging is the main risk factor for several neurodegenerative diseases. Increasing evidence from our lab and others show that aging results in changes in the inflammatory activation of microglial cells. This dysregulation results in an increased cytotoxicity, impaired phagocytosis, and promotion of neurodegenerative changes, all conditions that are observed in aged individuals. We found that in aging there is an increased inflammatory activation of glial cells as well as an increased basal activation of Smad2/3/4, the canonical pathway of the regulatory cytokine TGFβ, whereas Smad3 activation in response to inflammatory stimuli is reduced in aged animals. Among the many molecules involved in the regulation of glial cell activation, scavenger receptor class A (SR-A), which participate both in Aβ phagocytosis and the inflammatory activation of glial cells, appears to be a involved. Here we show by both in vitro and in ex vivo experiments that SR-A expression is decreased in aged individuals and through a Smad3-dependent mechanism after stimulation with TGFβ. Conditions of increased inflammatory activation can potentiate neurotoxicity, favoring neurodegenerative changes. Our results show that aging is associated with abnormal activation of TGFβ signaling, which promotes impairment of the scavenger function of microglia, and favors their cytotoxic activation and appears to led to neurodegenerative changes.

 

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