Impact of central and peripheral estrogen treatment on anxiety and depression phenotypes in a mouse model of postmenopausal obesity

Abstract

Obesity and diabetes increase the risk of depression, and the incidence of these conditions increases rapidly after menopause, but few animal models of postmenopausal obesity have been available. We developed a mouse model of postmenopausal obesity that exhibited anxiety and depressive phenotypes in behavioral tests. To examine the effect of estradiol (E2) in the model, we prepared 4 experimental groups: 1) control, sham-operated female C57BL/6 mice fed a regular diet; 2) OVX-HF, ovariectomized (OVX) mice fed a high-fat diet (HF); 3) E2-SC, OVX-HF mice administered subcutaneous (SC) E2 (50 μg/kg/day); and 4) E2-ICV, OVX-HF mice administered intracerebroventricular (ICV) E2 (1 μg/kg/day). OVX-HF mice exhibited anxiety phenotypes in the open field test, but not in the light-dark box test, and E2 treatment via both routes effectively ameliorated it. OVX-HF mice demonstrated depressive phenotypes in the tail suspension test and forced swim test. Both E2 treatments achieved significant improvement in the tail suspension test, but not in the forced swim test. Serum corticosterone levels did not differ among the groups. Hippocampal expression of glucocorticoid receptor mRNA and serotonin 1A receptor mRNA was significantly increased in OVX-HF mice and was decreased in E2-treated mice. The hypothalamic level of pro-brain-derived neurotrophic factor (proBDNF) protein was tended to decrease in OVX-HF mice, but neither E2 treatment increased it. Since this mouse model exhibited anxiety and depressive phenotypes in relatively short experimental periods without genetic manipulations, it would be useful for further exploring psychiatric phenotypes or screening of therapeutic candidates in postmenopausal obesity.

A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model

“…Estradiol has been known to reduce anxiety and depressive behavior along with restoration of BDNF levels in ovariectomized female rats. 26) Conversely, although estradiol improved the behavior of anxiety and depression in postmenopausal animal models, but it did not increase the expression of BDNF in the brain. 27) In addition, they compared the administration methods via subcutaneous (SC) and intracerebroventricular (ICV) route to examine therapeutic effect of estrogen on anxiety and depressive phenotypes in the postmenopausal mice model.…”

Pulsed administration for physiological estrogen replacement in mice

“…The fact that some women suffer from depression in the premenstrual, postpartum and perimenopausal periods is well documented 36,37 . Estradiol affects the central nervous system by promoting spontaneous physical activity, which supports lipolysis in the white adipose tissue and stimulates the reduction of body mass 28,38 . In this study, OVX mice that were tested for spontaneous locomotor activity, moved less and slower compared to the sham-operated control mice at 8 weeks post-surgery.…”

17β-Estradiol Attenuates Neuropathic Pain Caused by Spared Nerve Injury by Upregulating CIC-3 in the Dorsal Root Ganglion of Ovariectomized Rats

“…Rats were deprived of food overnight, and serum 17β-estradiol levels were assessed according to a previously described protocol (Homberg et al, 2018). Briefly, blood samples were collected from the abdominal aorta under anesthesia, and serum was separated by centrifugation at 15,000 r for 5 min.…”