title: Reactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog. [corrected].
abstract: As 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.
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, D-80336, Germany.
authors.forename: Swetlana
authors.initials: S
authors.lastname: Sirko
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Behrendt
authors.forename: Pia Annette
authors.initials: PA
authors.lastname: Johansson
authors.forename: Pratibha
authors.initials: P
authors.lastname: Tripathi
authors.forename: Marcos
authors.initials: M
authors.lastname: Costa
authors.forename: Sarah
authors.initials: S
authors.lastname: Bek
authors.forename: Christophe
authors.initials: C
authors.lastname: Heinrich
authors.forename: Steffen
authors.initials: S
authors.lastname: Tiedt
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.forename: Isabel Rebekka
authors.initials: IR
authors.lastname: Fischer
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Marina
authors.initials: M
authors.lastname: Snapyan
authors.forename: Armen
authors.initials: A
authors.lastname: Saghatelyan
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.forename: Kay
authors.initials: K
authors.lastname: Grobe
authors.forename: Leda
authors.initials: L
authors.lastname: Dimou
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D049109:Cell Proliferation; D002469:Cell Separation; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000150:complications / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
chemical_list: D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35)