Physical activity, but not environmental complexity, facilitates HPA axis response habituation to repeated audiogenic stress despite neurotrophin mRNA regulation in both conditions

Abstract

Stress exacerbates several physical and psychological disorders. Voluntary exercise can reduce susceptibility to many of these stress-associated disorders. In rodents, voluntary exercise can reduce hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to various stressors as well as upregulate several brain neurotrophins. An important issue regarding voluntary exercise is whether its effect on the reduction of HPA axis activation in response to stress is due to the physical activity itself or simply the enhanced environmental complexity provided by the running wheels. The present study compared the effects of physical activity and environmental complexity (that did not increase physical activity) on HPA axis habituation to repeated stress and modulation of brain neurotrophin mRNA expression. For six weeks, male rats were given free access to running wheels (exercise group), given 4 objects that were repeatedly exchanged (increased environmental complexity group), or housed in standard cages. On week 7, animals were exposed to 11 consecutive daily 30-min sessions of 98-dBA noise. Plasma corticosterone and adrenocorticotropic hormone were measured from blood collected directly after noise exposures. Tissue, including brains, thymi, and adrenal glands was collected on Day 11. Although rats in both the exercise and enhanced environmental complexity groups expressed higher levels of BDNF and NGF mRNA in several brain regions, only exercise animals showed quicker glucocorticoid habituation to repeated audiogenic stress. These results suggest that voluntary exercise, independent from other environmental manipulations, accounts for the reduction in susceptibility to stress.

Figure 1. Average Daily Running Distance over Course of Experiment

Average daily running distance (km) of exercised animals for weeks 1–8 of Experiment. Repeated stress exposures took place over weeks 7 and 8.

Figure 2. Mean Body Weight (g)+/− SEM Over Course of Experiment

Animals were weighed on days 1, 5, 12, 19, 26, 33, 40, 47, and 53 of experiment (noise began on day 43). Body weights were equivalent between groups on day 1, but were significantly lower in exercised animals on day 5 and thereafter compared to the other two groups, which did not differ from one another. #: Exercise group significantly different from home cage control and increased cage complexity groups, Tukey's HSD (p's < 0.05).

Figure 3. Plasma CORT Response to 98-dBA noise

Mean corticosterone concentrations (+/− SEM) of the exercise, increased cage complexity, and control groups over the successive days (1, 4, 8, and 11) of repeated loud noise stress. Exercised animals had overall lower CORT responses than control and increased complexity animals, suggesting that habituation was enhanced in exercised animals. #: Home cage control and increased environmental complexity groups significantly different from exercise group, Tukey's HSD (p's < 0.05).

Figure 4. Plasma ACTH Response to 98-dBA noise

Mean ACTH concentrations (+/− SEM) of the exercise, increased cage complexity, or control groups over the successive days (1, 4, 8, and 11) of repeated loud noise (98-dBA) stress. On day one, exercise animals had a reliably reduced ACTH response compared to increased cage complexity and control animals. Responses were statistically equivalent on each of the remaining sampling days. #: Exercise group significantly different from both control and increased cage complexity groups, Tukey's HSD (p'< 0.05).

Figure 5. BDNF mRNA Photomicrographs

Representative photomicrographs (taken from x-ray in situ films) of BDNF mRNA expression in the dorsal hippocampus of control (a), increased cage complexity (b) and exercise (c) animals. Note the increase in BDNF mRNA expression in increased cage complexity and exercise animals in different hippocampal subfields (CA3 and dentate gyrus).