Peripherally injected lipopolysaccharide induces apoptosis in the subventricular zone of young adult mice.
Because the subventricular zone (SVZ) constantly supplies newly generated neurons to the olfactory bulb (OB) along the rostral migratory stream (RMS) in adult brain, SVZ-RMS-OB axis has been thought to work as a unit. We previously reported that peripherally injected lipopolysaccharide (LPS) induces apoptosis in the OB in young adult mice. Therefore, this study was undertaken to examine whether peripherally injected LPS induces apoptotic cell death also in the SVZ. Two mouse strains were used: C3H/HeN and Toll-like receptor 4-mutated C3H/HeJ, and wild-type C57BL/6 and TNFR1(-/-)-2(-/-), in which the genes tumor necrosis factor receptor (TNFR)1 and TNFR2 are knocked out. Immunohistochemical study and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay done on the SVZ-RMS pathway of young adult male mice showed that peripherally injected LPS switches on the apoptotic signal by cleaving pro-caspase-3, thus possibly increasing the number of cells dying from apoptosis in these areas in adult mice. Activation of the tumor necrosis factor (TNF)-alpha-TNFR system played a critical role in fully inducing apoptosis in this pathway. We suggest that TNF-alpha was probably released not from microglia but from astrocytes in the SVZ and RMS.
Mori
Keiji
K
Department of Physiology, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan.
Kaneko
Yoko S
YS
Nakashima
Akira
A
Nagatsu
Toshiharu
T
Nagatsu
Ikuko
I
Ota
Akira
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002552:Cerebral Ventricles / Q000166:cytology* / Q000187:drug effects*; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3