Correlation between copper/zinc superoxide dismutase and the proliferation of neural stem cells in aging and following focal cerebral ischemia.
OBJECTIVE
Neural stem cells (NSCs) have been demonstrated in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus (DG). Although aging rats manifest a decrease in NSCs, rats exposed to stress (for example, ischemia, epilepsy, radiation, and trauma) show an increase in these cells. In transgenic mice, the overexpression of human copper/zinc superoxide dismutase (SOD1), an endogenous antioxidant, has been reported to be a protective enzyme against transient focal cerebral ischemia. The authors investigated the correlation between SOD1 and the proliferation of NSCs in aging as chronic oxidative stress (Experiment 1) and acute oxidative stress induced by transient focal cerebral ischemia (Experiment 2) in mice.


METHODS
Bromodeoxyuridine (BrdU) was used in the evaluation of NSCs. In Experiment 1, NSCs in the SVZ significantly increased in 16-month-old transgenic mice compared with wild-type mice (p = 0.0001). In Experiment 2, mice were subjected to 30-minute occlusions of the middle cerebral artery. The increase in NSCs in the DG in transgenic mice was significantly greater than that in wild-type mice (p < 0.05).


CONCLUSIONS
Results in this study suggest that chronic and acute oxidative stress may inhibit the proliferation of NSCs and that SOD1 may play a key role in NSC proliferation.
Takemura
Sunao
S
Department of Neurosurgery, Yamagata University School of Medicine, Yamagata, Japan. tkay2ma@med.id.yamagata-u.ac.jp
Kayama
Takamasa
T
Kuge
Atsushi
A
Ali
Hasmat
H
Kokubo
Yasuaki
Y
Sato
Shinya
S
Kamii
Hideyuki
H
Goto
Kaoru
K
Yoshimoto
Takashi
T
D000375:Aging / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology*; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons; D018384:Oxidative Stress; D013234:Stem Cells / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1