Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats.
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.
Zhu
Xin-Hong
XH
Department of Anatomy and Neurobiology, Southern Medical University, and Department of Radiation Oncology, Nanfang Hospital, Guangzhou 510515, China. zhuxh@fimmu.com
Yan
Hua-Cheng
HC
Zhang
Jie
J
Qu
Hong-Da
HD
Qiu
Xing-Sheng
XS
Chen
Liang
L
Li
Shu-Ji
SJ
Cao
Xiong
X
Bean
Jonathan C
JC
Chen
Long-Hua
LH
Qin
Xi-He
XH
Liu
Ji-Hong
JH
Bai
Xiao-Chun
XC
Mei
Lin
L
Gao
Tian-Ming
TM
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
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine