Elsevier

Neuroscience

Volume 133, Issue 3, 2005, Pages 853-861
Neuroscience

Systems neuroscience
Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus

https://doi.org/10.1016/j.neuroscience.2005.03.026Get rights and content

Abstract

Exercise is an important facet of behavior that enhances brain health and function. Increased expression of the plasticity molecule brain-derived neurotrophic factor (BDNF) as a response to exercise may be a central factor in exercise-derived benefits to brain function. In rodents, daily wheel-running exercise increases BDNF gene and protein levels in the hippocampus. However, in humans, exercise patterns are generally less rigorous, and rarely follow a daily consistency. The benefit to the brain of intermittent exercise is unknown, and the duration that exercise benefits endure after exercise has ended is unexplored. In this study, BDNF protein expression was used as an index of the hippocampal response to exercise. Both daily exercise and alternating days of exercise increased BDNF protein, and levels progressively increased with longer running duration, even after 3 months of daily exercise. Exercise on alternating days was as effective as daily exercise, even though exercise took place only on half as many days as in the daily regimen. In addition, BDNF protein remained elevated for several days after exercise ceased. Further, after prior exercise experience, a brief second exercise re-exposure insufficient to cause a BDNF change in naïve animals, rapidly reinduced BDNF protein to levels normally requiring several weeks of exercise for induction. The protein reinduction occurred with an intervening “rest” period as long as 2 weeks. The rapid reinduction of BDNF by an exercise stimulation protocol that is normally subthreshold in naïve animals suggests that exercise primes a molecular memory for BDNF induction. These findings are clinically important because they provide guidelines for optimizing the design of exercise and rehabilitation programs, in order to promote hippocampal function.

Section snippets

Animals

Adult male Sprague-Dawley rats (Charles-River Inc., MA, USA), 7–8 weeks of age (150–200g) at experimental onset, were individually housed with ad libitum access to food and water in a 12-h light/dark vivarium. Each cage of the exercising animals was individually equipped with a running wheel (Minimitter, OR, USA) that occupied 1/2 of the cage. Running activity was voluntary, and the nightly distance run was monitored by computer software (VitalView, Minimitter Co., OR, USA). For the

BDNF induction by daily vs intermittent exercise

To investigate the effect of different training paradigms on BDNF regulation, rats were allowed to exercise under two conditions of voluntary wheel-running: either daily access for 2, 4, 7, 14, or 28 days (Fig. 1A), or exercise on alternating-days over a period of 7, 14, 21, or 28 days (Fig. 1B). To assess the effect of long-term running on BDNF protein levels, an additional group of animals had daily wheel access for 3 months.

BDNF protein levels increased in response to both daily activity (F

Discussion

Several novel concepts emerge from this study. In particular, (1) intermittent exercise is as effective as daily exercise to increase BDNF protein levels, (2) BDNF protein remains elevated for several days after exercise has ceased, and (3) BDNF protein is rapidly reinduced to peak levels by a normally-subthreshold exercise re-exposure, even after 14 days of quiescence. Thus, the experience of BDNF induction by exercise is robust and long-lasting. Further, exercise experience increases the

Acknowledgments

This work was supported by R01-AG13411 to C.W.C.

References (47)

  • L. Tong et al.

    Effects of exercise on gene-expression profile in the rat hippocampus

    Neurobiol Dis

    (2001)
  • S. Vaynman et al.

    Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity

    Neuroscience

    (2003)
  • N.C. Berchtold et al.

    Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum

    J Neurosci Res

    (2002)
  • N.C. Berchtold et al.

    Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus

    Eur J Neurosci

    (2001)
  • K.B. Blomquist et al.

    Effects of physical conditioning on information-processing efficiency

    Percept Mot Skills

    (1987)
  • E. Carro et al.

    Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy

    J Neurosci

    (2001)
  • S. Colcombe et al.

    Fitness effects on the cognitive function of older adultsa meta-analytic study

    Psychol Sci

    (2003)
  • C.W. Cotman et al.

    Exercisea behavioral intervention to enhance brain health and plasticity

    Trends Neurosci

    (2002)
  • A. Figurov et al.

    Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus

    Nature

    (1996)
  • R.P. Friedland et al.

    Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members

    Proc Natl Acad Sci U S A

    (2001)
  • F. Gomez-Pinilla et al.

    Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity

    J Neurophysiol

    (2002)
  • B.N. Greenwood et al.

    Freewheel running prevents learned helplessness/behavioral depressionrole of dorsal raphe serotonergic neurons

    J Neurosci

    (2003)
  • O. Griesbeck et al.

    Combination of gene targeting and gene transfer by adenoviral vectors in the analysis of neurotrophin-mediated neuronal plasticity

    Cold Spring Harb Symp Quant Biol

    (1996)
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