PMID- 29137402 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220304 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 48 DP - 2017 Oct 13 TI - BDNF/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius. PG - 84028-84038 LID - 10.18632/oncotarget.21062 [doi] AB - Although compelling evidence indicates that estradiol (E2) acts in the nucleus tractus solitarius (NTS) to reduce food intake, the underlying mechanisms are largely unknown. We now report that estrogen's anorectic action occurs through enhancing the strength of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (TrkB) signaling in the NTS. Intra-4th-ventricular administration of a low dose of BDNF reduced food intake to a greater extent in ovariectomized (OVX) rats cyclically treated with E2 than in vehicle-treated OVX rats, implying that cyclic E2 replacement increases BDNF's satiating potency. OVX significantly decreased bdnf gene expression in the NTS, and this was reversed by cyclic replacement of E2. Treatment of cultured primary neuronal cells from embryonic rat brainstem with E2 or PPT (ERalpha agonist), but not with DPN (ERbeta agonist), significantly increased bdnf mRNA levels, indicating that ERalpha is the primary receptor mediating E2's stimulatory effect on bdnf gene expression. Administration of the selective TrkB antagonist, ANA-12, directly into the NTS significantly attenuated E2-induced reductions of food intake and body weight gain in OVX rats, indicating that TrkB receptor activation is necessary for E2's anorectic effect. Finally, relative to controls, OVX mice with bdnf gene knockdown specifically in the NTS had a blunted feeding response to E2. These data collectively imply that BDNF/TrkB receptor signaling in the NTS is a downstream mediator of E2 in the control of energy intake. FAU - Shen, Ling AU - Shen L AD - Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Wang, David Q H AU - Wang DQH AD - Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA. FAU - Xu, Meifeng AU - Xu M AD - Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Woods, Stephen C AU - Woods SC AD - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Liu, Min AU - Liu M AD - Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. LA - eng GR - R01 DK017844/DK/NIDDK NIH HHS/United States GR - R37 DK017844/DK/NIDDK NIH HHS/United States GR - R01 HL140962/HL/NHLBI NIH HHS/United States GR - R01 DK095440/DK/NIDDK NIH HHS/United States GR - R01 DK092779/DK/NIDDK NIH HHS/United States GR - P30 DK041296/DK/NIDDK NIH HHS/United States GR - R21 AA025737/AA/NIAAA NIH HHS/United States GR - R01 DK106249/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20170919 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5663574 OTO - NOTNLM OT - BDNF OT - TrkB receptor OT - estrogen OT - food intake OT - obesity COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest. EDAT- 2017/11/16 06:00 MHDA- 2017/11/16 06:01 PMCR- 2017/10/13 CRDT- 2017/11/16 06:00 PHST- 2017/07/18 00:00 [received] PHST- 2017/08/31 00:00 [accepted] PHST- 2017/11/16 06:00 [entrez] PHST- 2017/11/16 06:00 [pubmed] PHST- 2017/11/16 06:01 [medline] PHST- 2017/10/13 00:00 [pmc-release] AID - 21062 [pii] AID - 10.18632/oncotarget.21062 [doi] PST - epublish SO - Oncotarget. 2017 Sep 19;8(48):84028-84038. doi: 10.18632/oncotarget.21062. eCollection 2017 Oct 13.