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

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 (E 2 ), 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 E 2 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 E 2 . 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.

The effect of low- and moderate-intensity interval training on cognitive behaviors of male and female rats with VPA-induced autism

“…Interestingly, the effect of exercise on social interactions was sex-dependent, and moderate treadmill exercise reversely influenced the social behaviors of male autistic rats in contrast to female ones. In some cases, the difference in results between females and males can be attributed to gender-related factors, including sex hormones, behavioral variables, the change of the hypothalamic-pituitary-adrenal (HPA) axis activity, and the involvement of different neurotransmitters and brain areas [ 21 , 32 ]. For instance, the high activity of the HPA axis and disturbance in corticosterone levels can lead to substantial male-biased social behavior impairment [ 33 ].…”

“…The important role of sex hormones such as estrogen and progesterone in the developmental stages and neurotransmitter systems, along with their protective effects, should be taken into consideration by researchers for interpreting the sex-related differences [ 36 ]. It has been stated that estrogen and oxytocin levels in the brain may be responsible for reducing anxiety-like behaviors by treadmill exercise in female mice exposed to anxiety-inducing stress conditions [ 32 ]. A classic exploratory behavior recorded in the open field is rearing behavior, in which the animal temporarily stands on its hind legs to sample the environment.…”

Estrogen receptors mediate the antidepressant effects of aerobic exercise: A possible new mechanism

“…After ovariectomy, the mRNA expression of ERα and ERβ in the hippocampus of OVX rats decreased with a progressive decrease in estrogen levels (El-Khatib et al, 2020). Some studies have shown that improvement in depression-like behavior in OVX rats is partly attributed to the increased serum E2 levels after exercise (Lu et al, 2014), whereas several studies have reported no increase in plasma or serum estrogen levels in OVX rats after exercise (Choi et al, 2005;Rauf et al, 2015;He et al, 2021). Notably, a study showed that cerebellar estrogen levels were significantly higher after exercise (Rauf et al, 2015).…”

Mindfulness-Based Therapy in Patients with Breast Cancer with Depression and Anxiety: A Literature Review

“…Estrogen plays an essential role in regulating anxiety. Lack of estrogen corresponds to an increase in anxiety (Kalandakanond-Tongsong et al, 2012; He et al, 2021).…”