Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.
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.
Yamashita
Toru
T
Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Shinanomachi, Tokyo 160-8582, Japan.
Ninomiya
Mikiko
M
Hernández Acosta
Pilar
P
García-Verdugo
Jose Manuel
JM
Sunabori
Takehiko
T
Sakaguchi
Masanori
M
Adachi
Kazuhide
K
Kojima
Takuro
T
Hirota
Yuki
Y
Kawase
Takeshi
T
Araki
Nobuo
N
Abe
Koji
K
Okano
Hideyuki
H
Sawamoto
Kazunobu
K
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
D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D049452:Green Fluorescent Proteins