PMID- 12584730 OWN - NLM STAT- MEDLINE DCOM- 20030424 LR - 20091119 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 71 IP - 5 DP - 2003 Mar 1 TI - Tumor necrosis factor-alpha regulation of insulin-like growth factor-I, type 1 IGF receptor, and IGF binding protein expression in cerebellum of transgenic mice. PG - 721-31 AB - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF-I, which promotes CNS growth, TNF-alpha causes brain growth retardation and neural damage. Recently TNF-alpha has been shown to inhibit IGF-I signaling and actions in non-neural tissue. To investigate whether TNF-alpha deleteriously influences brain growth by altering the IGF-I system in vivo, we examined the expression of IGF-I, the type 1 IGF receptor (IGF1R) and IGF binding proteins (IGFBPs) in the brain of transgenic (Tg) mice with murine TNF-alpha overexpression. We show that overexpression of TNF-alpha reduces the weights of whole brain and all brain regions examined during development. In adult TNF-alpha Tg mice, cerebellum (CB) exhibited the greatest reduction in weight among the five brain regions examined, being approximately 77% of that in wild-type (WT) mice. IGF-I abundance was decreased in the CB, as well as in cerebral cortex and diencephalon, of TNF-alpha Tg mice. When compared to those in WT mice, CB IGF-I abundance in Tg mice was reduced by approximately 35%, approximately 45%, and approximately 40% at 2, 6, and 9 weeks of age, respectively. Of the IGFBPs studied the abundance of IGFBP-3 and IGFBP-4 was increased by 2-3.7-fold, and the abundance of IGFBP-5 was decreased by approximately 3-fold (as judged by Western immunoblot analysis). Histological analysis and immunocytochemical staining confirmed that TNF-alpha specifically increases IGFBP-3 and IGFBP-4 immunoreactivity, as well as that of the IGF1R, in radial glial and Purkinje cells. In addition, TNF-alpha alters CB cytoarchitecture, apparently by influencing granule cell migration. Our data indicate that TNF-alpha alters the expression of IGF-I system proteins in vivo, and suggest that altered expression of IGF-I system proteins may in part explain TNF-alpha deleterious actions on brain growth. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Ye, Ping AU - Ye P AD - Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ping_ye@med.unc.edu FAU - Price, Wayne AU - Price W FAU - Kassiotis, George AU - Kassiotis G FAU - Kollias, George AU - Kollias G FAU - D'Ercole, A Joseph AU - D'Ercole AJ LA - eng GR - NS38891/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Insulin-Like Growth Factor Binding Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Age Factors MH - Animals MH - Blotting, Western MH - Cell Movement/drug effects/genetics MH - Cerebellum/drug effects/growth & development/*metabolism MH - Immunohistochemistry MH - Insulin-Like Growth Factor Binding Proteins/*metabolism MH - Insulin-Like Growth Factor I/*metabolism MH - Mice MH - Mice, Transgenic MH - Neuroglia/cytology/metabolism MH - Organ Size/drug effects/genetics MH - Purkinje Cells/cytology/metabolism MH - Receptor, IGF Type 1/*metabolism MH - Tumor Necrosis Factor-alpha/*biosynthesis/genetics/pharmacology EDAT- 2003/02/14 04:00 MHDA- 2003/04/25 05:00 CRDT- 2003/02/14 04:00 PHST- 2003/02/14 04:00 [pubmed] PHST- 2003/04/25 05:00 [medline] PHST- 2003/02/14 04:00 [entrez] AID - 10.1002/jnr.10512 [doi] PST - ppublish SO - J Neurosci Res. 2003 Mar 1;71(5):721-31. doi: 10.1002/jnr.10512.