PMID- 30349488
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 9
DP  - 2018
TI  - Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF 
      Pathway in Postpartum Depression.
PG  - 434
LID - 10.3389/fpsyt.2018.00434 [doi]
LID - 434
AB  - Postpartum depression (PPD) is associated with mood disorders and elevated 
      inflammation. Studies have evidenced the activation/inhibition of autophagy and 
      excessive activation of microglia to have a close relationship with depression. 
      C57 and microglia-specific autophagy-deficient mice 
      (Cx3Cr1(Cre/+)ATG5(loxp/loxp)) were employed to establish the chronic unpredicted 
      mild stress depression mice model from embryonic day 7 (E7) to embryonic day 16 
      (E16). Fluoxetine was administered for 3 weeks (commencing from 1 week after 
      birth). Behavioral tests (open field, forced swimming, and sucrose preference 
      tests) were implemented. Western blot and immunofluorescence staining were 
      employed to assess the brain-derived neurotrophic factor (BDNF) expression level, 
      autophagy-associated proteins, and inflammatory factors. Depressive behavior was 
      reversed following fluoxetine treatment; this was evidenced via open field, 
      sucrose preference, and forced swimming tests. Both BDNF and autophagy-associated 
      proteins (ATG5, Beclin-1, and LC3II) were upregulated following fluoxetine 
      treatment. Inflammatory factors including nuclear factor kappa B and inducible 
      nitric oxide synthase were reduced while anti-inflammatory factor interleukin-10 
      (IL-10) was increased after fluoxetine treatment. Microglia-specific 
      autophagy-deficient mice (Cx3Cr1(Cre/+)ATG5(loxp/loxp)) showed a curtailed 
      autophagy level, higher inflammatory level, and reduced BDNF expression when 
      compared with C57 mice. Autophagy inhibition in microglia contributes to 
      inflammation, which further instigates PPD. Fluoxetine might mediate its 
      antidepressant effect in PPD through the autophagic pathway while upregulating 
      BDNF expression. In view of this, regulating BDNF in microglia is a potential 
      novel therapy target for PPD.
FAU - Tan, Xiaoning
AU  - Tan X
AD  - Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - Du, Xiaoxue
AU  - Du X
AD  - Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - Jiang, Yuting
AU  - Jiang Y
AD  - Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - Botchway, Benson O A
AU  - Botchway BOA
AD  - Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - Hu, Zhiying
AU  - Hu Z
AD  - Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou, 
      China.
FAU - Fang, Marong
AU  - Fang M
AD  - Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20181008
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC6186788
OTO - NOTNLM
OT  - brain-derived neurotrophic factor (BDNF)
OT  - chronic unpredicted mild stress
OT  - fluoxetine
OT  - inflammation
OT  - microglia
EDAT- 2018/10/24 06:00
MHDA- 2018/10/24 06:01
PMCR- 2018/10/08
CRDT- 2018/10/24 06:00
PHST- 2018/07/01 00:00 [received]
PHST- 2018/08/23 00:00 [accepted]
PHST- 2018/10/24 06:00 [entrez]
PHST- 2018/10/24 06:00 [pubmed]
PHST- 2018/10/24 06:01 [medline]
PHST- 2018/10/08 00:00 [pmc-release]
AID - 10.3389/fpsyt.2018.00434 [doi]
PST - epublish
SO  - Front Psychiatry. 2018 Oct 8;9:434. doi: 10.3389/fpsyt.2018.00434. eCollection 
      2018.