title: Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats.
abstract: Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressant-like effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.
authors.affiliation: Department of Anatomy and Neurobiology, Southern Medical University, and Department of Radiation Oncology, Nanfang Hospital, Guangzhou 510515, China. zhuxh@fimmu.com
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Zhu
authors.forename: Hua-Cheng
authors.initials: HC
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Hong-Da
authors.initials: HD
authors.lastname: Qu
authors.forename: Xing-Sheng
authors.initials: XS
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Shu-Ji
authors.initials: SJ
authors.lastname: Li
authors.forename: Xiong
authors.initials: X
authors.lastname: Cao
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Bean
authors.forename: Long-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Xi-He
authors.initials: XH
authors.lastname: Qin
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Liu
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Bai
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine