Peripheral lipopolysaccharide induces apoptosis in the murine olfactory bulb

The olfactory bulb (OB) is one of the few structures in the adult mammalian CNS that contains a continuous supply of newly generated neurons in the subventricular zone. Therefore, the balance between the supply of new cells and apoptosis in the OB might determine olfactory function. Lipopolysaccharide-induced tumor necrosis factor (TNF)-alpha triggers the apoptotic cascade mediated by the TNF/TNF receptor (TNFR) pathway. The present study therefore examines the effect of the propagated innate immune reaction triggered by peripheral lipopolysaccharide on the OB of C3H/HeN mice. Within 2 h of an intraperitoneal injection of lipopolysaccharide, mRNA expression levels of the genes encoding IkappaB, TNF-alpha, and TNFR type 1 in the mouse OB were significantly enhanced. Double immunofluorescence microscopy confirmed that almost all TNF-alpha-immunopositive cells in the OB of the TNF-injected mice were located in the subependymal zone and that they overlapped cells immunostained with antibody against glial fibrillary acidic protein, but not with the antibody against F4/80, an antigenic marker of microglia. The number of TUNEL-positive cells identified exclusively in the granule cell layer was significantly increased in mice injected with lipopolysaccharide and sacrificed at 24 h thereafter. These results suggest that peripheral lipopolysaccharide causes disequilibrium between the supply and disappearance of the cells in the OB, which might lead to olfactory dysfunction.