Regulation of GDF-15, a distant TGF-β superfamily member, in a mouse model of cerebral ischemia

• Verfasst von: Schindowski, Katharina [VerfasserIn]
• Verfasst von: von Bohlen und Halbach, Oliver [VerfasserIn]
• Verfasst von: Strelau, Jens [VerfasserIn]
• Verfasst von: Ridder, Dirk [VerfasserIn]
• Verfasst von: Herrmann, Oliver [VerfasserIn]
• Verfasst von: Schober, Andreas [VerfasserIn]
• Verfasst von: Schwaninger, Markus [VerfasserIn]
• Verfasst von: Unsicker, Klaus [VerfasserIn]
• Titel: Regulation of GDF-15, a distant TGF-β superfamily member, in a mouse model of cerebral ischemia
• Verf.angabe: Katharina Schindowski, Oliver von Bohlen und Halbach, Jens Strelau, Dirk A. Ridder, Oliver Herrmann, Andreas Schober, Markus Schwaninger, Klaus Unsicker
• Jahr: 2011
• Umfang: 11 S.
• Fussnoten: Published online: 3 December 2010 ; Gesehen am 11.10.2022
• Titel Quelle: Enthalten in: Cell & tissue research
• Ort Quelle: Berlin : Springer, 1924
• Jahr Quelle: 2011
• Band/Heft Quelle: 343(2011), 2, Seite 399-409
• ISSN Quelle: 1432-0878
• DOI: doi:10.1007/s00441-010-1090-5
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cortex
• Sach-SW: Expression
• Sach-SW: GDF-15 knockout
• Sach-SW: Growth/differentiation factor-15
• Sach-SW: Hippocampus
• Sach-SW: Ischemia
• Sach-SW: Mouse (adult, male, C57BL/6)
• Sach-SW: Occlusion of the middle cerebral artery
• K10plus-PPN: 181858249X

Abstract

GDF-15 is a novel distant member of the TGF-β superfamily and is widely distributed in the brain and peripheral nervous system. We have previously reported that GDF-15 is a potent neurotrophic factor for lesioned dopaminergic neurons in the substantia nigra, and that GDF-15-deficient mice show progressive postnatal losses of motor and sensory neurons. We have now investigated the regulation of GDF-15 mRNA and immunoreactivity in the murine hippocampal formation and selected cortical areas following an ischemic lesion by occlusion of the middle cerebral artery (MCAO). MCAO prominently upregulates GDF-15 mRNA in the hippocampus and parietal cortex at 3 h and 24 h after lesion. GDF-15 immunoreactivity, which is hardly detectable in the unlesioned brain, is drastically upregulated in neurons identified by double-staining with NeuN. NeuN staining reveals that most, if not all, neurons in the granular layer of the dentate gyrus and pyramidal layers of the cornu ammonis become GDF-15-immunoreactive. Moderate induction of GDF-15 immunoreactivity has been observed in a small number of microglial cells identified by labeling with tomato lectin, whereas astroglial cells remain GDF-15-negative after MCAO. Comparative analysis of the size of the infarcted area after MCAO in GDF-15 wild-type and knockout mice has failed to reveal significant differences. Together, our data substantiate the notion that GDF-15 is prominently upregulated in the lesioned brain and might be involved in orchestrating post-lesional responses other than the trophic support of neurons.