title: Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice.
abstract: Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China; Department of Anesthesiology, Jiangsu Province Hospital, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China; Department of Physiology, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China; Department of Physiology, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China; Department of Physiology, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Obstetrics and Gynecology, Hangzhou First People's Hospital, Hangzhou 860571, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jiangsu Province Hospital, Nanjing Medical University, Nanjing 86025, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 86025, China; Department of Physiology, Nanjing Medical University, Nanjing 86025, China. Electronic address: lingchen@njmu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000209:etiology* / Q000378:metabolism; D000089662:Doublecortin Protein; D004958:Estradiol / Q000172:deficiency* / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy / Q000009:adverse effects / Q000523:psychology; D049590:Postpartum Period / Q000187:drug effects / Q000502:physiology / Q000523:psychology*; D011247:Pregnancy
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D004958:Estradiol
keywords: Brain-derived neurotrophic factor (BDNF); Estradiol benzoate (EB); Hormone-simulated pregnancy (HSP); NMDA receptor (NMDAr); Neurogenesis; Postpartum depression (PPD)