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Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety.

Pan-Vazquez A, Rye N, Ameri M, McSparron B, Smallwood G, Bickerdyke J, Rathbone A, Dajas-Bailador F, Toledo-Rodriguez M - Mol Brain (2015)

Bottom Line: The opposite was found for pair-housed animals.Single-housing increased the time spent on stretch attend postures.However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs.

View Article: PubMed Central - PubMed

Affiliation: Queens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.

ABSTRACT

Background: Lack of physical activity and increased levels of stress contribute to the development of multiple physical and mental disorders. An increasing number of studies relate voluntary exercise with greater resilience to psychological stress, a process that is highly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanisms underlying the beneficial effects of exercise on stress resilience are still poorly understood. Here we have studied the impact of long term exercise and housing conditions on: a) hippocampal expression of glucocorticoid receptor (Nr3c1), b) epigenetic regulation of Nr3c1 (DNA methylation at the Nr3c1-1F promoter and miR-124 expression), c) anxiety (elevated plus maze, EPM), and d) adrenal gland weight and adrenocorticotropic hormone receptor (Mc2r) expression.

Results: Exercise increased Nr3c1 and Nr3c1-1F expression and decreased miR-124 levels in the hippocampus in single-housed mice, suggesting enhanced resilience to stress. The opposite was found for pair-housed animals. Bisulfite sequencing showed virtually no DNA methylation in the Nr3c1-1F promoter region. Single-housing increased the time spent on stretch attend postures. Exercise decreased the time spent at the open arms of the EPM, however, the mobility of the exercise groups was significantly lower. Exercise had opposite effects on the adrenal gland weight of single and pair-housed mice, while it had no effect on adrenal Mc2r expression.

Conclusions: These results suggest that exercise exerts a positive impact on stress resilience in single-housed mice that could be mediated by decreasing miR-124 and increasing Nr3c1 expression in the hippocampus. However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs.

No MeSH data available.


Related in: MedlinePlus

Effect of exercise and housing conditions on adrenal gland weight and adrenal Mc2r expression. Expression for single-housed mice and pair-housed that either exercised or remained sedentary. a Adrenal gland weight and bMc2r expression. # p < 0.05
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Fig6: Effect of exercise and housing conditions on adrenal gland weight and adrenal Mc2r expression. Expression for single-housed mice and pair-housed that either exercised or remained sedentary. a Adrenal gland weight and bMc2r expression. # p < 0.05

Mentions: The adrenal gland is a stress responsive organ. While it is involved in the response to stressful stimulus (as part of the HPA axis), it is also affected by chronic stress (which usually increases adrenal weight) [25]. Thus, we determined whether housing or exercise had any effect on adrenal gland weight and/or adrenocorticotropic hormone receptor (Mr2c) expression at the adrenal glands. We found that exercise has opposite effects on adrenal weight depending on housing conditions. Two-way ANOVA showed a significant housing*exercise interaction for the adrenal gland weight [F (1,26) = 8.921 p = 0.006]. Post hoc comparisons indicated that pair-housed mice that exercised had significantly lighter adrenals than sedentary pair-housed mice [t (12.75) = −2.571 p = 0.033] (Fig. 6a) and single-housed mice that exercised [t (14) = −2.648 p = 0.019] (Fig. 6a). The exercise-induced increase in adrenal weight in single-housed mice is probably due to physical activity, as exercise leads to an acute increase in corticosterone. This could be beneficial, as previous studies have suggested that the increase in adrenal size in response to exercise is related to a higher sensitivity to changes in the HPA axis, producing faster decays in glucocorticoid levels in response to stress and ultimately improving stress resilience [55]. The increase in adrenal weight in the sedentary pair-housed mice possibly results from the increase in stress due to pair-housing as suggested by the Nr3c1 results. The decrease in adrenal weight in animals pair-housed that exercise seems more puzzling. We could hypothesize that it is due to adrenal “burnout” by excessive corticosterone release, resulting from the combined effects of exercise and stress. Finally we found that neither exercise nor housing affected Mc2r expression in the adrenal gland (Fig. 6b). This is in agreement with studies by Droste et al. in the rat showing that 4 weeks voluntary running resulted in increase hippocampal Nr3c1 without change in ACTH response to stress [56, 57].Fig. 6


Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety.

Pan-Vazquez A, Rye N, Ameri M, McSparron B, Smallwood G, Bickerdyke J, Rathbone A, Dajas-Bailador F, Toledo-Rodriguez M - Mol Brain (2015)

Effect of exercise and housing conditions on adrenal gland weight and adrenal Mc2r expression. Expression for single-housed mice and pair-housed that either exercised or remained sedentary. a Adrenal gland weight and bMc2r expression. # p < 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487841&req=5

Fig6: Effect of exercise and housing conditions on adrenal gland weight and adrenal Mc2r expression. Expression for single-housed mice and pair-housed that either exercised or remained sedentary. a Adrenal gland weight and bMc2r expression. # p < 0.05
Mentions: The adrenal gland is a stress responsive organ. While it is involved in the response to stressful stimulus (as part of the HPA axis), it is also affected by chronic stress (which usually increases adrenal weight) [25]. Thus, we determined whether housing or exercise had any effect on adrenal gland weight and/or adrenocorticotropic hormone receptor (Mr2c) expression at the adrenal glands. We found that exercise has opposite effects on adrenal weight depending on housing conditions. Two-way ANOVA showed a significant housing*exercise interaction for the adrenal gland weight [F (1,26) = 8.921 p = 0.006]. Post hoc comparisons indicated that pair-housed mice that exercised had significantly lighter adrenals than sedentary pair-housed mice [t (12.75) = −2.571 p = 0.033] (Fig. 6a) and single-housed mice that exercised [t (14) = −2.648 p = 0.019] (Fig. 6a). The exercise-induced increase in adrenal weight in single-housed mice is probably due to physical activity, as exercise leads to an acute increase in corticosterone. This could be beneficial, as previous studies have suggested that the increase in adrenal size in response to exercise is related to a higher sensitivity to changes in the HPA axis, producing faster decays in glucocorticoid levels in response to stress and ultimately improving stress resilience [55]. The increase in adrenal weight in the sedentary pair-housed mice possibly results from the increase in stress due to pair-housing as suggested by the Nr3c1 results. The decrease in adrenal weight in animals pair-housed that exercise seems more puzzling. We could hypothesize that it is due to adrenal “burnout” by excessive corticosterone release, resulting from the combined effects of exercise and stress. Finally we found that neither exercise nor housing affected Mc2r expression in the adrenal gland (Fig. 6b). This is in agreement with studies by Droste et al. in the rat showing that 4 weeks voluntary running resulted in increase hippocampal Nr3c1 without change in ACTH response to stress [56, 57].Fig. 6

Bottom Line: The opposite was found for pair-housed animals.Single-housing increased the time spent on stretch attend postures.However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs.

View Article: PubMed Central - PubMed

Affiliation: Queens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.

ABSTRACT

Background: Lack of physical activity and increased levels of stress contribute to the development of multiple physical and mental disorders. An increasing number of studies relate voluntary exercise with greater resilience to psychological stress, a process that is highly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanisms underlying the beneficial effects of exercise on stress resilience are still poorly understood. Here we have studied the impact of long term exercise and housing conditions on: a) hippocampal expression of glucocorticoid receptor (Nr3c1), b) epigenetic regulation of Nr3c1 (DNA methylation at the Nr3c1-1F promoter and miR-124 expression), c) anxiety (elevated plus maze, EPM), and d) adrenal gland weight and adrenocorticotropic hormone receptor (Mc2r) expression.

Results: Exercise increased Nr3c1 and Nr3c1-1F expression and decreased miR-124 levels in the hippocampus in single-housed mice, suggesting enhanced resilience to stress. The opposite was found for pair-housed animals. Bisulfite sequencing showed virtually no DNA methylation in the Nr3c1-1F promoter region. Single-housing increased the time spent on stretch attend postures. Exercise decreased the time spent at the open arms of the EPM, however, the mobility of the exercise groups was significantly lower. Exercise had opposite effects on the adrenal gland weight of single and pair-housed mice, while it had no effect on adrenal Mc2r expression.

Conclusions: These results suggest that exercise exerts a positive impact on stress resilience in single-housed mice that could be mediated by decreasing miR-124 and increasing Nr3c1 expression in the hippocampus. However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs.

No MeSH data available.


Related in: MedlinePlus