title: A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse.
abstract: Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Magnusson
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Göritz
authors.affiliation: Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Jemal
authors.initials: J
authors.lastname: Tatarishvili
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: David O
authors.initials: DO
authors.lastname: Dias
authors.affiliation: Division of Translational Cancer Research, Lund University, SE-223 63 Lund, Sweden.
authors.forename: Emma M K
authors.initials: EM
authors.lastname: Smith
authors.affiliation: Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.affiliation: Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden. jonas.frisen@ki.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Frisén
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D017353:Gene Deletion; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497762:Notch1 protein, mouse; C497571:Rbpj protein, mouse; D051881:Receptor, Notch1