title: Tumor necrosis factor and its p55 and p75 receptors are not required for axonal lesion-induced microgliosis in mouse fascia dentata.
abstract: Tumor necrosis factor (TNF) is a potent pro-inflammatory and neuromodulatory cytokine. In the CNS it is produced primarily by microglia and considered to regulate microglial activation. On the basis of previous observations of increased microglial TNF mRNA synthesis in areas of anterograde axonal and terminal degeneration in mice, we studied the effect of TNF and its p55 and p75 receptors on axonal lesion-induced microglial activation in fascia dentata following transection of the perforant path (PP) projection. Unexpectedly, cell counting showed that the axonal lesion-induced microglial response in TNF and TNF-p55p75 receptor knock out mice and C57BL/6 mice was similar 5 days after the lesion. In addition, the microglial expression of the lysosomal-associated antigen CD68, and the clearance of MBP(+) myelin debris appeared similar in TNF and TNF-p55p75 receptor knock out mice compared to C57BL/6 mice. Quantitative PCR and in situ hybridization showed the expression of TNF mRNA to be maximally upregulated 6 h after the lesion, and confirmed that TNF mRNA was still upregulated 5 days after lesion when microglial numbers, CD11b mRNA level, and cellular TNF-p55 and -p75 receptor mRNA level reached maximum. However, in spite of the induction of TNF mRNA, TNF protein level remained at base-line in fascia dentata using immunohistochemistry and ELISA. In conclusion, the results showed a lower than expected lesion-induced increase in TNF protein, and that neither TNF nor its receptors were required for the axonal lesion-induced microglial morphological transformation and proliferation or for the initial clearance of degenerated myelin in the PP-deafferented fascia dentata.
authors.affiliation: Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark. cfenger@health.sdu.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Fenger
authors.forename: Nina
authors.initials: N
authors.lastname: Drojdahl
authors.forename: Martin
authors.initials: M
authors.lastname: Wirenfeldt
authors.forename: Lene
authors.initials: L
authors.lastname: Sylvest
authors.forename: Ole Steen
authors.initials: OS
authors.lastname: Jorgensen
authors.forename: Michael
authors.initials: M
authors.lastname: Meldgaard
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lambertsen
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000473:pathology; D019771:Axotomy; D018845:CD11 Antigens / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism* / Q000503:physiopathology; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology; D005911:Gliosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D019580:Perforant Pathway / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014855:Wallerian Degeneration / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule