Long-term supplementation of dehydroepiandrosterone improved depressive-like behaviors by increasing BDNF expression in the hippocampus in ovariectomized rats

Siyang Wu; Mei Ye; Zhulin Li; Shizhong Bu; Yisheng Zhang

doi:10.1016/j.heliyon.2020.e05180

Long-term supplementation of dehydroepiandrosterone improved depressive-like behaviors by increasing BDNF expression in the hippocampus in ovariectomized rats

Heliyon. 2020 Oct 8;6(10):e05180. doi: 10.1016/j.heliyon.2020.e05180. eCollection 2020 Oct.

Authors

Siyang Wu^{1

2}, Mei Ye¹, Zhulin Li¹, Shizhong Bu², Yisheng Zhang¹

Affiliations

¹ Department of Gynaecology and Obstetrics, Ningbo Medical Treatment Center, Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315040, PR China.
² Zhejiang Provincial Key Lab of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, PR China.

Abstract

Objective: Dehydroepiandrosterone (DHEA), a precursor of estrogen, partially exhibits its biological effect after conversion to estrogen. Its biological significance in perimenopausal depressive disorder or postpartum depression remains unknown. Here, we observed the effects of long-term supplementation of DHEA on depression-like behaviors in ovariectomized rats.

Methods: We established the model as one of sex hormone deficiency in female rats by bilateral ovariectomy. We observed the effects of 13.3 mg/kg DHEA or 0.27 mg/kg estradiol were given daily by gavage for 12 weeks on lipid metabolism, glucose tolerance, and depression-like behaviors in ovariectomized rats. Furthermore, the expression of brain-derived neurotrophic factor (BDNF) and its signaling molecule in the hippocampus was analyzed.

Results: The 12-week supplementation of DHEA or estradiol significantly alleviated weight gain and improved the glucose tolerance in the ovariectomized rats. Moreover, Long-term supplement of DHEA or estradiol significantly increased sucrose preference and locomotion activities, and reduced immobility duration of the ovariectomized rats in the water. Both DHEA and estradiol treatments increased the expression of BDNF, phosphorylation of ERK and CREB, and ERβ, but not that of ERα in the hippocampus of the ovariectomized rats.

Conclusions: Overall, chronic treatment with DHEA improved depression-like behaviors in ovariectomized rats, suggesting that it may be useful for the treatment of sex hormone deficiency such as perimenopausal depressive disorder or postpartum depression.

Keywords: Brain-derived neurotrophic factor; Dehydroepiandrosterone; Depression; Estrogen receptors; Gynecology; Health sciences; Hippocampus; Neuroscience; Nutrient availability; Perimenopausal depressive disorder; Pharmacology.