title: Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.
abstract: Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.
authors.affiliation: Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Shinanomachi, Tokyo 160-8582, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Pilar
authors.initials: P
authors.lastname: Hernández Acosta
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sunabori
authors.forename: Masanori
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Adachi
authors.forename: Takuro
authors.initials: T
authors.lastname: Kojima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawase
authors.forename: Nobuo
authors.initials: N
authors.lastname: Araki
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sawamoto
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005455:Fluorescent Antibody Technique / Q000379:methods; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery; D020547:Lateral Ventricles / Q000166:cytology*; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D049452:Green Fluorescent Proteins