Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

Emily E. Noble, Vijayakumar Mavanji, Morgan R. Little, Charles J Billington, Catherine M Kotz, ChuanFeng Wang

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51 Scopus citations


Background: Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods: To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16. weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for 7. weeks of exercise intervention. Results: Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes ( p<. 0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions: These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalNeurobiology of Learning and Memory
StatePublished - Oct 2014

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health , and the Department of Veterans Affairs . Additional support was provided by Award Number T32DK083250 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDDK or the National Institutes of Health. We would like to thank Martha Grace for her laboratory assistance.


  • BDNF
  • High-fat diet
  • Hippocampus
  • Memory
  • Running wheel
  • Treadmill
  • Two-way active avoidance


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