Elsevier

Life Sciences

Volume 72, Issue 12, 7 February 2003, Pages 1421-1436
Life Sciences

Dependence of rat hippocampal c-Fos expression on intensity and duration of exercise

https://doi.org/10.1016/S0024-3205(02)02406-2Get rights and content

Abstract

The expression of c-Fos, an immediately early gene, is a marker of neural activity. In the present study, the effect of treadmill exercise on c-Fos expression was investigated in various regions of the rat hippocampus via immunohistochemistry. The first part of the experiment was aimed at determining the dependence of c-Fos expression on the intensity of treadmill exercise. In most of the hippocampal regions studied, increasing c-Fos expression was observed with increasing exercise intensity. In the second part of the experiment, the dependence of c-Fos expression on the duration of treadmill exercise was investigated. The c-Fos expression induced by mild-intensity exercise increased until the 7th day of exercise and subsequently decreased. Results of the present study suggest that the effect of treadmill exercise on neuronal activity in the hippocampus is intensity-and duration-dependent.

Introduction

The beneficial effects of exercise on the brain functions have been reported in numerous studies. Physical exercise is known to alleviate the deleterious effects of aging and neurodegenerative diseases, to reduce vulnerability to brain damage under various pathologic conditions [1], and to facilitate functional recovery following cerebral ischemia [2], [3]. It is generally accepted that exercise facilitates spatial learning involving the hippocampus [4] and has a protective effect against cognitive impairment and dementia, in particular of the Alzheimer type [5].

Brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus is induced by physical exercise [6], and exercise-induced upregulation of neurotrophins, including BDNF, increases resistance to brain damage and neurodegeneration of aging [6], [7]. Exercise also enhances cell proliferation and/or neurogenesis [8] and neuronal plasticity and changes the levels of transcription of various genes, resulting in increases in neuronal activity and synaptic remodeling [9]. It has been reported that age-related decline in insulin-like growth factor I (IGF-I)-dependent neurogenesis contributes to the cognitive changes of aging [10], and exercise prevents and protects against brain damage by enhancing the uptake of circulating IGF-I [1], [11], [12].

The c-Fos protein, encoded by the immediately early gene c-fos [13], is known to be a transcription factor and a functional marker of neuronal activity [14], [15]. It has been reported that expression of c-fos gene is induced by various stressful stimuli; such as immunological challenges [16], [17], hemorrhage [16], [18], noise [14], [16], immobilization [19], and pedal shock stimulus [20], [21].

It has been reported that treadmill exercise and forced swimming increase c-Fos expression in the hippocampus and the medial nucleus of the amygdala [16], [22]. However, the intensity- and duration-dependence of the effect of treadmill exercise on c-Fos expression has not been reported yet. In the present study, the intensity- and duration-dependence of the effect of treadmill exercise on c-Fos expression in the rat hippocampus was investigated via immunohistochemistry.

Section snippets

Animals and treatments

Male Sprague-Dawley rats weighing 160 ± 10 g (5 weeks of age) were used in the experiment. The experimental procedures were performed in accordance with the animal care guidelines of NIH and the Korean Academy of Medical Sciences. The animals were housed at a controlled temperature (20 ± 2 °C) and maintained under light–dark cycles, each consisting of 12 h of light and 12 h of darkness (lights on from 07:00 to 19:00 h), with food and water made available ad libitum.

Intensity-dependence of the effect of treadmill exercise on c-Fos expression

The first part of the

Intensity-dependence of the effect of treadmill exercise on c-Fos expression in the CA1 region

The number of Fos-positive cells in the hippocampal CA1 region was about 94.19 ± 6.40 per section in the control group, 273.25 ± 9.17 in the mild-exercise group, 326.69 ± 18.10 in the moderate-exercise group, and 382.38 ± 13.81 in the severe-exercise group. c-Fos expression in the CA1 region of the hippocampus thus appears to have increased with increasing exercise intensity (Fig. 1).

Intensity-dependence of the effect of treadmill exercise on c-Fos expression in the CA2 and CA3 regions

The number of Fos-positive cells in the hippocampal CA2 and CA3 regions was about 61.69 ± 3.18 per section in

Discussion

The intensity- and duration-dependence of the effect of treadmill exercise on c-Fos expression in various regions of the hippocampus was investigated. In addition, the intensity-dependence of the effect of treadmill exercise on GR expression in the hippocampal CA1 region was investigated in the present study. Expression of c-Fos in the CA1, CA2, CA3, dentate gyrus, and hilus was shown to increase with increasing exercise intensity, and the maximum level was reached on the 7th day of exercise,

Conclusion

In the present study, c-Fos expression was shown to increase in various regions of the hippocampus with increasing exercise intensity, and this rise was shown to continue until the 7th day of exercise, after which the level of expression declined. Based on the results of the present study, it can be suggested that treadmill exercise enhances neuronal activity in the hippocampus in an intensity-and duration-dependent manner.

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