Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD)

Author(s)

Pestana-Oliveira, Nayara ^[1] ; Kalil, Bruna ^[2] ; Leite, Cristiane Mota ^[2] ; Gomes Carolino, Ruither Oliveira ^[2] ; Debarba, Lucas Kniess ^[1] ; Kagohara Elias, Lucila Leico ^[1] ; Antunes-Rodrigues, Jose ^[1] ; Anselmo-Franci, Janete A. ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: ENEURO; v. 5, n. 1 JAN-FEB 2018.
• Web of Science Citations: 3

Abstract

Chronic exposure to 4-vinylcycloxene diepoxide (VCD) in rodents accelerates the natural process of ovarian follicular atresia modelling perimenopause in women. We investigated why estrogen therapy is beneficial for symptomatic women despite normal or high estrogen levels during perimenopause. Female rats (28 d) were injected daily with VCD or oil for 15 d; 55-65 d after the first injection, pellets of 17 beta-estradiol or oil were inserted subcutaneously. Around 20 d after, the rats were euthanized (control rats on diestrus and estradiol-treated 21 d after pellets implants). Blood was collected for hormone measurement, the brains were removed and dorsal raphe nucleus (DRN), hippocampus (HPC), and amygdala (AMY) punched out for serotonin (5-HT), estrogen receptor beta (ER beta), and progesterone receptor (PR) mRNA level measurements. Another set of rats was perfused for tryptophan hydroxylase (TPH) immunohistochemistry in the DRN. Periestropausal rats exhibited estradiol levels similar to controls and a lower progesterone level, which was restored by estradiol. The DRN of periestropausal rats exhibited lower expression of PR and ER beta mRNA and a lower number of TPH cells. Estradiol restored the ER beta mRNA levels and number of serotonergic cells in the DRN caudal subregion. The 5-HT levels were lower in the AMY and HPC in peristropausal rats, and estradiol treatment increased the 5-HT levels in the HPC and also increased ER beta expression in this area. In conclusion, estradiol may improve perimenopause symptoms by increasing progesterone and boosting serotonin pathway from the caudal DRN to the dorsal HPC potentially through an increment in ER beta expression in the DRN. (AU)

• FAPESP's process: 14/09772-9 - Hormonal profile, response to stress and anxiety assessment in an animal model of perimenopause.
• Grantee: Janete Aparecida Anselmo Franci
• Support Opportunities: Regular Research Grants