title: Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats.
abstract: Perimenopausal syndromes begin as ovarian function ceases and the most common symptoms are hot flushes. Data indicate that the projections of serotonin to hypothalamus may be involved in the mechanism of hot flushes. Therefore, the aim of this study is to investigate the potential role of the serotonin dorsal raphe-preoptic hypothalamus pathway for hot flushes in an animal model of menopause. We determined the changes in serotonin expression in the dorsal raphe (DR) and preoptic anterior hypothalamus (POAH) in ovariectomized rats. We also explored the therapeutical effects of estradiol valerate and Remifemin in this model. Eighty female Sprague-Dawley rats were randomly assigned to sham-operated (SHAM) group, ovariectomy (OVX) group with vehicle, ovariectomy with estradiol valerate treatment (OVX+E) group and ovariectomy with Remifemin (OVX+ICR) group. Serotonin expression was evaluated in the DR and POAH using immunofluorescence and quantified in the DR using an enzyme-linked immunosorbent assay (ELISA). Apoptosis was analyzed in the DR by TUNEL assay. The number of serotonin immunoreactive neurons and the level of serotonin expression in the DR decreased significantly following OVX compared to the SHAM group. No TUNEL-positive cells were detected in the DR in any group. In addition, following OVX, the number of serotonin-positive fibers decreased significantly in the ventromedial preoptic nucleus (VMPO), especially in the ventrolateral preoptic nucleus (VLPO). Treatment with either estradiol or Remifemin for 4 weeks countered the OVX-induced decreases in serotonin levels in both the DR and the hypothalamus, with levels in the treated rats similar to those in the SHAM group. A fluorescently labeled retrograde tracer was injected into the VLPO at the 4-week time point. A significantly lower percentage of serotonin with CTB double-labeled neurons in CTB-labeled neurons was demonstrated after ovariectomy, and both estradiol and Remifemin countered this OVX-induced decrease. We conclude that serotonin pathway is changed after ovariectomy, including the serotonin synthesis in DR and serotonin fibers in PO/AH, both E and Remifemin have an equivalent therapeutic effect on it.
authors: Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Wenjuan
authors: W
authors: Wang
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China; Obstetrics and Gynecology Department, Civil Aviation General Hospital, No. 1 Gaojingjia Street, Chaoyang District, Beijing, China.
authors: Guangxia
authors: G
authors: Cui
authors: Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Biao
authors: B
authors: Jin
authors: Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Ke
authors: K
authors: Wang
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Xing
authors: X
authors: Chen
authors: Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
authors: Yu
authors: Y
authors: Sun
authors: Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. Electronic address: qinlihua88@163.com.
authors: Lihua
authors: L
authors: Qin
authors: Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China. Electronic address: bwp66@163.com.
authors: Wenpei
authors: W
authors: Bai
mesh_terms: D000818:Animals; D031885:Cimicifuga; D065847:Dorsal Raphe Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008593:Menopause / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D010052:Ovariectomy; D010936:Plant Extracts / Q000008:administration & dosage*; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000166:cytology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D010936:Plant Extracts; C073419:Remifemin; D012701:Serotonin; D004958:Estradiol
keywords: Dorsal raphe (DR); Estradiol valerate; Ovariectomy; Preoptic anterior hypothalamus (POAH); Remifemin; Serotonin pathway