Navegando por Autor "Heinrich, Christophe"
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Artigo Evidence of progenitor cell lineage rerouting in the adult mouse hippocampus after status epilepticus(Frontiers in Neuroscience, 2020-09-18) Moura, Daniela Maria de Sousa; Brandão, Juliana Alves; Lentini, Celia; Heinrich, Christophe; Queiroz, Claudio Marcos Teixeira de; Costa, Marcos RomualdoCell lineage in the adult hippocampus comprises multipotent and neuron-committed progenitors. In the present work, we fate-mapped neuronal progenitors using Dcx-CreERT2 and CAG-CAT-EGFP double-transgenic mice (cDCX/EGFP). We show that 3 days after tamoxifen-mediated recombination in cDCX/EGFP adult mice, GFP+ cells in the dentate gyrus (DG) co-expresses DCX and about 6% of these cells are proliferative neuronal progenitors. After 30 days, 20% of GFP+ generated from these progenitors differentiate into GFAP+ astrocytes. Unilateral intrahippocampal administration of the chemoconvulsants kainic acid (KA) or pilocarpine (PL) triggered epileptiform discharges and led to a significant increase in the number of GFP+ cells in both ipsi and contralateral DG. However, while PL favored the differentiation of neurons in both ipsi- and contralateral sides, KA stimulated neurogenesis only in the contralateral side. In the ipsilateral side, KA injection led to an unexpected increase of astrogliogenesis in the Dcx-lineage. We also observed a small number of GFP+/GFAP+ cells displaying radial-glia morphology ipsilaterally 3 days after KA administration, suggesting that some Dcx-progenitors could regress to a multipotent stage. The boosted neurogenesis and astrogliogenesis observed in the Dcx-lineage following chemoconvulsants administration correlated, respectively, with preservation or degeneration of the parvalbuminergic plexus in the DG. Increased inflammatory response, by contrast, was observed both in the DG showing increased neurogenesis or astrogliogenesis. Altogether, our data support the view that cell lineage progression in the adult hippocampus is not unidirectional and could be modulated by local network activity and GABA-mediated signalingArtigo Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog(2013-04-04) Sirko, Swetlana; Behrendt, Gwendolyn; Johansson, Pia Annette; Tripathi, Pratibha; Costa, Marcos Romualdo; Bek, Sarah; Heinrich, Christophe; Tiedt, Steffen; Colak, Dilek; Dichgans, Martin; Fischer, Isabel Rebekka; Plesnila, Nikolaus; Staufenbiel, Matthias; Haass, Christian; Snapyan, Marina; Saghatelyan, Armen; Li-Huei, Tsai; Fischer, André; Grobe, Kay; Dimou, Leda; Götz, MagdalenaAs a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, we had demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In the present study, we demonstrate that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog (SHH) is the signal that acts directly on the astrocytes and is necessary and sufficient to elicit the stem cell response both in vitro and in vivo. These findings provide a molecular basis for how cells with neural stem cell lineage emerge at sites of brain injury and imply that the high levels of SHH known to enter the brain from extraneural sources after invasive injury can trigger this response.