Role of microglial SIRT2 on neuroinflammation

Sirtuin 2 (SIRT2) has been associated with aging, age-related pathologies and neuroinflammation. In the present study, we have analyzed in mice the implication of microglial sirtuin 2 in two different models of neuroinflammation: an acute pro-inflammatory stimulus (intraperitoneal injection of LPS) and neurodegeneration (mouse model of Alzheimer disease). To this end, we have generated a conditional knock out mouse model of SIRT2, specifically in microglia, and we analyzed the molecular consequences (specifically the expression of different glial markers) of such genetic deletion in these two models. Our results show that in the former case SIRT2KO microglia are morphologically different after LPS treatment which suggests that their function may be different and that they have a different capacity to response against a pro-inflammatory stimulus. In the context of a neurodegenerative disease, specifically AD, microglial SIRT2 deletion induces a reduction in the survival and a worsening in the abeta pathology in 5 months old-APP/PS1 mice.