Peripheral lipopolysaccharide induces apoptosis in the murine olfactory bulb

• Published in: Brain research Vol. 1039; no. 1; pp. 116 - 129
• Main Authors: Mori, Keiji, Kaneko, Yoko S., Nakashima, Akira, Nagatsu, Ikuko, Takahashi, Hisahide, Ota, Akira
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.03.2005
• Subjects: Animals; Apoptosis; Apoptosis - immunology; I-kappa B Kinase; Immunohistochemistry; Injections, Intraperitoneal; Lipopolysaccharide; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Male; Mice; Mice, Inbred C3H; Olfactory bulb; Olfactory Bulb - cytology; Olfactory Bulb - immunology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptors, Tumor Necrosis Factor, Type I - genetics; Receptors, Tumor Necrosis Factor, Type I - immunology; Receptors, Tumor Necrosis Factor, Type I - metabolism; RNA, Messenger - analysis; Rostral migratory stream; Signal Transduction - immunology; Tissue Distribution; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Lipopolysaccharide; Disorders of the nervous system; Olfactory bulb; Rostral migratory stream; Tumor necrosis factor-α; Apoptosis
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2005.01.078

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.