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

• Published in: PloS one 2018-12, Vol.13 (12), p.e0209859
• Main Authors: Wada, Tsutomu, Sameshima, Azusa, Yonezawa, Rika, Morita, Mayuko, Sawakawa, Kanae, Tsuneki, Hiroshi, Sasaoka, Toshiyasu, Saito, Shigeru
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adolescent depression; Age; Animal models; Animals; Anxiety; Anxiety - chemically induced; Anxiety - drug therapy; Anxiety - metabolism; Anxiety - physiopathology; Biology and Life Sciences; Brain; Brain-derived neurotrophic factor; Care and treatment; Corticosterone; Depression - chemically induced; Depression - drug therapy; Depression - metabolism; Depression - physiopathology; Diabetes mellitus; Diet; Dietary Fats - adverse effects; Dietary Fats - pharmacology; Disease Models, Animal; Emotional disorders; Estrogen antagonists; Estrogens; Estrogens - therapeutic use; Female; Field tests; Gene expression; Glucocorticoids; Gynecology; Health aspects; Health risks; High fat diet; Hippocampus; Hormone Replacement Therapy; Hypothalamus; Infusions, Intraventricular; Injections, Subcutaneous; Laboratory rats; Medicine and Health Sciences; Memory; Menopause; Mental depression; Metabolism; Mice; mRNA; Neurosciences; Obesity; Obesity - chemically induced; Obesity - drug therapy; Obesity - metabolism; Obesity - physiopathology; Obstetrics; Open-field behavior; Ovariectomy; Pharmacology; Phenotype; Phenotypes; Post-menopause; Postmenopause - metabolism; Proteins; Research and Analysis Methods; Rodents; Serotonin; Sex hormones; Social Sciences
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0209859

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.