TY - JOUR
T1 - Peripheral lipopolysaccharide induces apoptosis in the murine olfactory bulb
AU - Mori, Keiji
AU - Kaneko, Yoko S.
AU - Nakashima, Akira
AU - Nagatsu, Ikuko
AU - Takahashi, Hisahide
AU - Ota, Akira
N1 - Funding Information:
This work was supported by grants-in-aid from Fujita Health University, JAPAN, to AO and KM. We thank Ms. Rié Chiba, Ms. Saori Tanaka, Ms. Sayoko Nishio, and Ms. Kasumi Okazaki for their technical help.
PY - 2005/3/28
Y1 - 2005/3/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.brainres.2005.01.078
DO - 10.1016/j.brainres.2005.01.078
M3 - Article
C2 - 15781053
AN - SCOPUS:15244350255
SN - 0006-8993
VL - 1039
SP - 116
EP - 129
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -