Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice

Feng-Qin He; Mei-Yang Fan; Yu-Nan Hui; Rui-Juan Lai; Xin Chen; Ming-Juan Yang; Xiao-Xia Cheng; Zi-Jian Wang; Bin Yu; Bing-Jie Yan; Zhen Tian

doi:10.1016/j.ibneur.2021.10.001

Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice

IBRO Neurosci Rep. 2021 Oct 8:11:164-174. doi: 10.1016/j.ibneur.2021.10.001. eCollection 2021 Dec.

Authors

Feng-Qin He^{1

2}, Mei-Yang Fan^{1

2}, Yu-Nan Hui^{1

2}, Rui-Juan Lai^{1

2}, Xin Chen^{1

2}, Ming-Juan Yang^{1

2}, Xiao-Xia Cheng^{1

2}, Zi-Jian Wang^{1

2}, Bin Yu^{1

2}, Bing-Jie Yan^{1

2}, Zhen Tian^{1

2}

Affiliations

¹ Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.
² Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China.

Abstract

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E₂), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there's increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E₂ levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E₂. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Keywords: BNST, bed nucleus of the stria terminalis; CVMS, chronic variable moderate stress; Chronic variable moderate stress (CVMS); E2, 17-beta-oestradiol; ELISA, enzyme-linked immunosorbent assay; EPM, elevated plusmazetest; ERα-IRs, estrogen receptors αimmunoreactive neurons; ERβ-IRs, estrogen receptor β immunoreactive neurons; Estrogen receptor α (ERα); Estrogen receptor β (ERβ); HPA, hypothalamic–pituitary–adrenal; HRP, horseradishperoxidase; HTRE, higher speed TRE; LMTRE, low-moderate speed TRE; MeA, medial amygdaloid nucleus; OF, open field test; OT-IRs, Oxytocin immunoreactive neurons; Oxytocin (OT); PBS, phosphatebufferedsolution; PVN, paraventricular nucleus; SON, supraoptic nucleus; TRE, treadmill exercise; Treadmill exercise (TRE); mPOA, medial preopticarea.