title: PML regulates neuroprotective innate immunity and neuroblast commitment in a hypoxic-ischemic encephalopathy model.
abstract: Regulation of innate immune responses and activation of tissue regenerative processes are key elements in the pathophysiology of brain injuries. The promyelocytic leukemia (PML) gene was originally identified on a breakpoint of chromosomal translocation t(15;17) associated with acute PML. We have studied the role of PML protein during acute and regenerative phases after hypoxia-ischemia (HI) in brains of neonatal mice. We found that PML prevents tissue loss and apoptotic cell death selectively in subcortical regions of the brain at early stages after damage. In accordance with this, we revealed that PML is important for microglia activation and production of key inflammatory cytokines such as IL1α, IL1β, IL1RN, CXCL10, CCL12 and TNFα. During the regenerative phase, PML-depleted mice were found to have impaired transformation of transit-amplifying precursors into migratory progenitors. This was accompanied by increased ratios of symmetric versus asymmetric neural progenitor cell divisions during tissue repair and a specific defect in tissue restoration within the striatum 42 days after HI. The data demonstrate a dual role of PML in protection and recovery after brain injury.
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.|Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Vuk
authors.initials: V
authors.lastname: Palibrk
authors.affiliation: Department of Microbiology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Rajikala
authors.initials: R
authors.lastname: Suganthan
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.|Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Katja
authors.initials: K
authors.lastname: Scheffler
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.|Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.|Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Microbiology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Stig Ove
authors.initials: SO
authors.lastname: Bøe
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D063990:Gene Ontology; D020925:Hypoxia-Ischemia, Brain / Q000276:immunology* / Q000473:pathology*; D007113:Immunity, Innate; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism; D000066829:Neuroprotection; D000071156:Promyelocytic Leukemia Protein / Q000378:metabolism*; D012038:Regeneration; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D000071156:Promyelocytic Leukemia Protein; D055748:SOXB1 Transcription Factors