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Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice

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Abstract

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

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Acknowledgments

This work was supported by grants of the National Research Foundation of Korea funded by the Korean Government (NRF-2013R1A1A2062984).

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The authors have no conflict of interest.

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Authors and Affiliations

  1. School of Art and Physical Education, Andong University, Songcheon-dong, Andong-si, Gyeongsangbuk-do, 760-749, Republic of Korea

    Tae-Kyung Han

  2. Department of Physical Education, Dankook University, Cheonan-si, Chungnam-do, 330-951, Republic of Korea

    Jang-Kyu Lee

  3. Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan-si, Chungnam-do, 330-951, Republic of Korea

    Yea-Hyun Leem

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  1. Tae-Kyung Han
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Correspondence to Yea-Hyun Leem.

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Tae-Kyung Han and Jang-Kyu Lee contributed equally to this work.

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Han, TK., Lee, JK. & Leem, YH. Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice. Metab Brain Dis 30, 711–718 (2015). https://doi.org/10.1007/s11011-014-9624-2

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