Early-life lipopolysaccharide exposure potentiates forebrain expression of NLRP3 inflammasome proteins and anxiety-like behavior in adolescent rats.

ABSTRACT

BACKGROUND: Neonatal inflammation may affect brain development and lead to cognitive and emotional deficits at adolescence and adulthood. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is the core component of NLRP3 inflammasome, which may involve in neuroinflammation. We explored if early-life exposure to the bacterial endotoxin lipopolysaccharide (LPS) could promote the expression of proteins related to NLRP3 inflammasome, including NLRP3, the apoptosis-associated speck-like protein (ASC) and cysteiny aspartate-specific protease (Caspase-1) in the forebrain, and behavioral alteration in adolescent rats. METHODS: Two-week old Sprague Dawley rats were divided into naïve control, vehicle (phosphate buffered saline, PBS) control and LPS (100µg/kg, i.p.) treatment groups. Anxiety and depression-like behaviors were examined around 1month age, with the expression of NLRP3, ASC and Caspase-1 in the prefrontal cortex (PFC) and hippocampus analyzed by means of immunohistochemistry and western blot. RESULTS: LPS-treated rats exhibited anxiety but not depressive-like behavior as indicated by results of open field, elevated plus maze, dark-light box, sucrose preference and forced swimming tests. Increased immunolabeling of NLRP3, ASC and Caspase-1 in neurons and/or microglia occurred in the PFC and hippocampus in LPS-treated adolescents relative to controls, with immunoblot shown elevated levels of these proteins. CONCLUSION: Early-life inflammatory stress promotes the expression of NLRP3 inflammasome proteins in the brain and the occurrence of anxiety-like behavior in adolescent rats.