Peripherally injected lipopolysaccharide induces apoptosis in the subventricular zone of young adult mice

• Published in: Neuroscience letters Vol. 481; no. 2; pp. 126 - 130
• Main Authors: Mori, Keiji, Kaneko, Yoko S., Nakashima, Akira, Nagatsu, Toshiharu, Nagatsu, Ikuko, Ota, Akira
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 06.09.2010; Elsevier
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Astrocytes; Biological and medical sciences; Brain; Caspase 3 - metabolism; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cerebral Ventricles - cytology; Cerebral Ventricles - drug effects; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; In Situ Nick-End Labeling - methods; Lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microtubule-Associated Proteins - metabolism; Nervous system; Neural Pathways - drug effects; Neural Pathways - physiology; Neurogenesis; Neuropeptides - metabolism; Olfactory bulb; Olfactory system and olfaction. Gustatory system and gustation; Receptors, Tumor Necrosis Factor, Type I - deficiency; Receptors, Tumor Necrosis Factor, Type II - deficiency; Rostral migratory stream; Subventricular zone; Toll-like receptors; Tumor necrosis factor receptors; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: nervous system and sense organs; Lipopolysaccharide; Olfactory bulb; Rostral migratory stream; Subventricular zone; Apoptosis; Rodentia; Central nervous system; Encephalon; Vertebrata; Mammalia; Olfactory pathway; Mouse; Cell death; Animal
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.06.070

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)-α-TNFR system played a critical role in fully inducing apoptosis in this pathway. We suggest that TNF-α was probably released not from microglia but from astrocytes in the SVZ and RMS.