title: Differential roles of TNFR1 and TNFR2 signaling in adult hippocampal neurogenesis.
abstract: Tumor necrosis factor alpha (TNFα) is a potent inhibitor of neurogenesis in vitro but here we show that TNFα signaling has both positive and negative effects on neurogenesis in vivo and is required to moderate the negative impact of cranial irradiation on hippocampal neurogenesis. In vitro, basal levels of TNFα signaling through TNFR2 are required for normal neural progenitor cell proliferation while basal signaling through TNFR1 impairs neural progenitor proliferation. TNFR1 also mediates further reductions in proliferation and elevated cell death following exposure to recombinant TNFα. In vivo, TNFR1(-/-) and TNFα(-/-) animals have elevated baseline neurogenesis in the hippocampus, whereas absence of TNFR2 decreases baseline neurogenesis. TNFα is also implicated in defects in neurogenesis that follow radiation injury but we find that loss of TNFR1 has no protective effects on neurogenesis and loss of TNFα or TNFR2 worsened the effects of radiation injury on neurogenesis. We conclude that the immunomodulatory signaling of TNFα mediated by TNFR2 is more significant to radiation injury outcome than the proinflammatory signaling mediated through TNFR1.
authors: Stanford University, Institute for Stem Cell Biology and Regenerative Medicine, Lorry I. Lokey Stem Cell Building, G1141, 265 Campus Drive, Stanford, CA 94305, United States. chenzhiguo@gmail.com
authors: Zhiguo
authors: Z
authors: Chen
authors: Theo D
authors: TD
authors: Palmer
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D016371:Cranial Irradiation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D055495:Neurogenesis / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse
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