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.
Mori
Keiji
K
Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Kaneko
Yoko S
YS
Nakashima
Akira
A
Nagatsu
Ikuko
I
Takahashi
Hisahide
H
Ota
Akira
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051550:I-kappa B Kinase; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009830:Olfactory Bulb / Q000166:cytology / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse