The NLRP3 inflammasome is constitutively expressed in macrophages and microglia, the resident macrophages of the central nervous system (CNS). Microglia are monocytic in origin and migrate to the CNS during early embryonic development (Kaushik et al., 2012). Microglia are ubiquitous throughout the brain, with the highest concentration in the hippocampus (Block et al., 2007; Lawson et al., 1990; Perry et al., 1985). Preliminary results from our group have shown that acute restraint stress leads to activation of the NLRP3 inflammasome in the hippocampus (Iwata et al., 2012). We are currently extending this work using NLRP3 knockout mice to examine the functional impact of the NLRP3 inflammasome in the actions of stress. The maturation and release of IL-1β is significantly reduced in NLRP3 null mutant mice (Hanamsagar et al., 2011; Martinon et al., 2006), and we predict that the molecular and behavioral effects of stress will be decreased in these mice. Pharmacological inhibitors of the NLRP3 inflammasome, such as the antidiabetic drug glyburide, may also prove effective in blocking the elevation of IL-1β in response to stress and depression (Lamkanfi et al., 2009).
