Role of TLR4 in olfactory-based spatial learning activity of neonatal mice after developmental exposure to diesel exhaust origin secondary organic aerosol

Exposure to ambient air pollutants has been reported to have various adverse health impacts. Ambient particulate matter comprises primary particles released directly via engine exhaust and secondary organic aerosols (SOAs) formed from oxidative reactions of the ultrafine particle fraction of diesel exhaust (DE). Toll-like receptor 4 (TLR4) is well known to initiate the inflammatory cascade in the central nervous system. However, whether and how DE and DE-SOA exposure influences TLR4 signaling in the immature brain remains unclear. We attempted to evaluate the roles of TLR-4, inflammatory mediators and microglial markers in the impaired spatial learning ability of neonatal mice exposed to DE and DE-SOAs. Pregnant C3H/HeN (TLR4-intact) and C3H/HeJ (TLR4- mutated) mice were exposed to clean air, DE or DESOA from gestational day 14 to postnatal day (PND) 10 (5 h/day for 5 days) in exposure chambers. PND11 neonatal mice were examined for their performance in the olfactory-based spatial learning tes