Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Extracellular Superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation

Yani Zou, Rikki Corniola, David Leu, Aslam Khan, Peyman Sahbaie, Ayanabha Chakraborti, David J. Clark, John R. Fike and Ting-Ting Huang
Proceedings of the National Academy of Sciences of the United States of America
Vol. 109, No. 52 (December 26, 2012), pp. 21522-21527
Stable URL: http://www.jstor.org/stable/42553702
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Extracellular Superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation
Preview not available

Abstract

Cranial irradiation is widely used in cancer therapy, but it often causes cognitive defects in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. However, in an earlier study mice deficient in the antioxidant enzyme extracellular Superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation-induced defects in hippocampal functions. To further dissect the role of EC-SOD in neurogenesis and in response to irradiation, we generated a bigenic EC-SOD mouse model (OE mice) that expressed high levels of EC-SOD in mature neurons in an otherwise EC-SOD-deficient environment. EC-SOD deficiency was associated with reduced progenitor cell proliferation in the subgranular zone of dentate gyrus in KO and OE mice. However, high levels of EC-SOD in the granule cell layer supported normal maturation of newborn neurons in OE mice. Following irradiation, wild-type mice showed reduced hippocampal neurogenesis, reduced dendritic spine densities, and defects in cognitive functions. OE and KO mice, on the other hand, were largely unaffected, and the mice performed normally in neurocognitive tests. Although the resulting hippocampal-related functions were similar in OE and KO mice following cranial irradiation, molecular analyses suggested that they may be governed by different mechanisms: whereas neurotrophic factors may influence radiation responses in OE mice, dendritic maintenance may be important in the KO environment. Taken together, our data suggest that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions, and that highlevel EC-SOD may provide protection against irradiation-related defects in hippocampal functions.

Page Thumbnails

  • Thumbnail: Page 
[21522]
    [21522]
  • Thumbnail: Page 
21523
    21523
  • Thumbnail: Page 
21524
    21524
  • Thumbnail: Page 
21525
    21525
  • Thumbnail: Page 
21526
    21526
  • Thumbnail: Page 
21527
    21527