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Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation.

Publication ,  Journal Article
Wong-Goodrich, SJE; Pfau, ML; Flores, CT; Fraser, JA; Williams, CL; Jones, LW
Published in: Cancer research
November 2010

Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to 4 months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting 1 month after sham or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdUrd) immunolabeling and enzyme-linked immunosorbent assay indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdUrd+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor-1, and occurred despite irradiation-induced elevations in hippocampal proinflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention.

Duke Scholars

Published In

Cancer research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

November 2010

Volume

70

Issue

22

Start / End Page

9329 / 9338

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Time Factors
  • Running
  • Radiation Dosage
  • Physical Conditioning, Animal
  • Oncology & Carcinogenesis
  • Neurogenesis
  • Mice, Inbred C57BL
  • Mice
  • Memory Disorders
 

Citation

APA
Chicago
ICMJE
MLA
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Wong-Goodrich, S. J. E., Pfau, M. L., Flores, C. T., Fraser, J. A., Williams, C. L., & Jones, L. W. (2010). Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer Research, 70(22), 9329–9338. https://doi.org/10.1158/0008-5472.can-10-1854
Wong-Goodrich, Sarah J. E., Madeline L. Pfau, Catherine T. Flores, Jennifer A. Fraser, Christina L. Williams, and Lee W. Jones. “Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation.Cancer Research 70, no. 22 (November 2010): 9329–38. https://doi.org/10.1158/0008-5472.can-10-1854.
Wong-Goodrich SJE, Pfau ML, Flores CT, Fraser JA, Williams CL, Jones LW. Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer research. 2010 Nov;70(22):9329–38.
Wong-Goodrich, Sarah J. E., et al. “Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation.Cancer Research, vol. 70, no. 22, Nov. 2010, pp. 9329–38. Epmc, doi:10.1158/0008-5472.can-10-1854.
Wong-Goodrich SJE, Pfau ML, Flores CT, Fraser JA, Williams CL, Jones LW. Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation. Cancer research. 2010 Nov;70(22):9329–9338.

Published In

Cancer research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

November 2010

Volume

70

Issue

22

Start / End Page

9329 / 9338

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Time Factors
  • Running
  • Radiation Dosage
  • Physical Conditioning, Animal
  • Oncology & Carcinogenesis
  • Neurogenesis
  • Mice, Inbred C57BL
  • Mice
  • Memory Disorders