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)-α 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 IκB, TNF-α, and TNFR type 1 in the mouse OB were significantly enhanced. Double immunofluorescence microscopy confirmed that almost all TNF-α-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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology