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Phosphoinositide 3‐kinase promotes adult subventricular neuroblast migration after stroke
Author(s) -
Katakowski Mark,
Zhang Zheng Gang,
Chen Jieli,
Zhang Ruilan,
Wang Ying,
Jiang Hao,
Zhang Lijie,
Robin Adam,
Li Yi,
Chopp Michael
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10775
Subject(s) - subventricular zone , neuroblast , rostral migratory stream , olfactory bulb , microbiology and biotechnology , pi3k/akt/mtor pathway , protein kinase b , biology , ly294002 , neural stem cell , neuroscience , signal transduction , chemistry , neurogenesis , stem cell , central nervous system
Rodent adult subventricular zone (SVZ)‐derived progenitor cells abandon the rostral migratory stream (RMS)/olfactory complex postmiddle cerebral artery occlusion (MCAo) and migrate into compromised tissue, possibly playing a role in brain recovery. Using SVZ tissue explants from the adult rat, we investigated the role of the phosphoinositide 3‐kinase (PI3K) signal transduction pathway in the migration of SVZ cells. Stroke significantly ( P < .01) increased migratory speed (198 ± 39 μm/day) of neuroblasts out of the SVZ explants compared with the speed (99 ± 20 μm/day) in the normal SVZ (nSVZ) explants within the first 3 days of incubation. Three‐dimensional laser scanning confocal microscopy revealed formation of neuroblast encompassing chain‐like astrocyte structures extruding from both normal and stroke explants. Western blots showed that stroke SVZ (sSVZ) explants increased Akt phosphorylation. Treatment of sSVZ explants with the selective PI3K inhibitor LY294002 significantly ( P < .01) attenuated neuroblast migration and Akt phosphorylation, whereas treatment with LY294002 did not affect the number of bromodeoxyuridine (BrdU)‐ and caspase‐3‐immunoreactive cells, indicating that stroke‐enhanced neuroblast migration is independent of cell proliferation and survival. PI3K catalyzes phosphatidylinositol‐3,4,5‐triphosphate (PIP 3 ) which facilitates Akt phosphorylation. Thus, our data demonstrate that the PI3K/Akt signal transduction pathway mediates neuroblast migration after stroke. © 2003 Wiley‐Liss, Inc.