Effects of altered levels of extracellular superoxide dismutase and irradiation on hippocampal neurogenesis in female mice.
OBJECTIVE
Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study.


METHODS
Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined.


RESULTS
Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level.


CONCLUSIONS
In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, California.
Yani
Y
Zou
David
D
Leu
Jennifer
J
Chui
John R
JR
Fike
Ting-Ting
TT
Huang
D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D016371:Cranial Irradiation; D018891:Dentate Gyrus / Q000098:blood supply / Q000528:radiation effects; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D006624:Hippocampus / Q000528:radiation effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055806:Microvessels / Q000528:radiation effects; D058953:Neural Stem Cells / Q000166:cytology / Q000528:radiation effects; D055495:Neurogenesis / Q000502:physiology / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D020933:Neurotrophin 3 / Q000378:metabolism / Q000528:radiation effects; D011836:Radiation Tolerance / Q000502:physiology; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D013482:Superoxide Dismutase