PMID- 31820273
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 17
IP  - 2
DP  - 2020 Apr
TI  - FG-4592 Improves Depressive-Like Behaviors through HIF-1-Mediated Neurogenesis 
      and Synapse Plasticity in Rats.
PG  - 664-675
LID - 10.1007/s13311-019-00807-3 [doi]
AB  - Depression, plus the accompanying memory impairment, is one of the leading causes 
      of disability worldwide. Thus, there is a critical need to develop new drugs 
      based on distinct strategies. FG-4592, an inhibitor of prolyl hydroxylase, 
      activates the hypoxia-inducible factor-1 (HIF-1) pathway, to produce multiple 
      effects on cell properties. Here, we examined whether FG-4592 has antidepressant 
      effects, using a chronic unpredictable mild stress (CUMS) procedure to establish 
      rodent depression models. We found that FG-4592 not only reversed depressive 
      behaviors but also improved CUMS-induced memory impairment. Mechanistically, 
      FG-4592 could play an important role in promoting hippocampal neurogenesis and 
      synaptic plasticity. At the molecular level, FG-4592 was found to activate HIF-1 
      and cAMP-responsive element-binding protein/brain-derived neurotrophic factor 
      signaling pathways in vivo, as well as promote the expression of postsynaptic 
      density (PSD) proteins, PSD95 and Homer1. An examination of primary hippocampal 
      neurons showed that FG-4592 promoted dendritic growth. Taken together, our 
      results not only provide an experimental basis for the future application of 
      FG-4592 in clinical treatment of depression but also support the argument that 
      the HIF-1 signaling pathway is a promising target for the treatment of 
      depression.
FAU - Li, Gaifen
AU  - Li G
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
AD  - Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 
      100069, China.
FAU - Zhao, Ming
AU  - Zhao M
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
FAU - Cheng, Xiang
AU  - Cheng X
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
FAU - Zhao, Tong
AU  - Zhao T
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
FAU - Feng, Zhenlong
AU  - Feng Z
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
FAU - Zhao, Yongqi
AU  - Zhao Y
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China.
FAU - Fan, Ming
AU  - Fan M
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China. fanmingchina@126.com.
AD  - Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 
      100069, China. fanmingchina@126.com.
AD  - Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, 
      China. fanmingchina@126.com.
FAU - Zhu, Lingling
AU  - Zhu L
AUID- ORCID: 0000-0002-2220-2231
AD  - Institute of Military Cognition and Brain Sciences, Academy of Military Medical 
      Sciences, Beijing, 100850, China. linglingzhu@hotmail.com.
AD  - Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 
      100069, China. linglingzhu@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Antidepressive Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Isoquinolines)
RN  - TE7660XO1C (Glycine)
RN  - X3O30D9YMX (roxadustat)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Behavior, Animal/drug effects
MH  - Depression/etiology/*metabolism
MH  - Glycine/*analogs & derivatives/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Isoquinolines/*pharmacology
MH  - Male
MH  - Neurogenesis/*drug effects
MH  - Neuronal Plasticity/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stress, Psychological/complications
PMC - PMC7283439
OTO - NOTNLM
OT  - CUMS
OT  - FG-4592
OT  - HIF-1
OT  - Neurogenesis
OT  - Synapse plasticity
EDAT- 2019/12/11 06:00
MHDA- 2021/06/05 06:00
PMCR- 2021/04/01
CRDT- 2019/12/11 06:00
PHST- 2019/12/11 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2019/12/11 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - S1878-7479(23)01365-X [pii]
AID - 807 [pii]
AID - 10.1007/s13311-019-00807-3 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2020 Apr;17(2):664-675. doi: 10.1007/s13311-019-00807-3.