PMID- 24434771
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20140303
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 263
DP  - 2014 Mar 28
TI  - Etazolate abrogates the lipopolysaccharide (LPS)-induced downregulation of the 
      cAMP/pCREB/BDNF signaling, neuroinflammatory response and depressive-like 
      behavior in mice.
PG  - 1-14
LID - S0306-4522(14)00012-8 [pii]
LID - 10.1016/j.neuroscience.2014.01.008 [doi]
AB  - Increasing evidence has indicated that immune challenge by bacterial 
      lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory 
      response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically 
      hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential 
      PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior 
      remains unclear. Here using a model of depression induced by the repeated 
      administration of LPS during 16days, and then investigated the influence of LPS 
      on the expression of PDE4, interleukin-1beta (IL-1beta) and antidepressant action of 
      etazolate in mice through forced swimming, novelty suppressed feeding, sucrose 
      preference and open-field tests. Our results showed that etazolate pretreatment 
      facilitated the recovery from weight loss and prevented the depressive-like 
      behavior induced by repeated LPS administration. Moreover, the antidepressant 
      action of etazolate was paralleled by significantly reducing the expression 
      levels of PDE4A, PDE4B, PDE4D and IL-1beta and up-regulating the cAMP/phosphorylated 
      cAMP response-element binding protein (pCREB)/brain-derived neurotrophic factor 
      (BDNF) signaling in the hippocampus and prefrontal cortex of mice. These results 
      indicate that the effects of etazolate on the depressive-like behavior induced by 
      repeated LPS treatment may partially depend on the inhibition of PDE4 subtypes, 
      the activation of the cAMP/pCREB/BDNF signaling and the anti-inflammatory 
      responses in the hippocampus and prefrontal cortex.
CI  - Crown Copyright (c) 2014. Published by Elsevier Ltd. All rights reserved.
FAU - Guo, J
AU  - Guo J
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China.
FAU - Lin, P
AU  - Lin P
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China.
FAU - Zhao, X
AU  - Zhao X
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China.
FAU - Zhang, J
AU  - Zhang J
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China.
FAU - Wei, X
AU  - Wei X
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China.
FAU - Wang, Q
AU  - Wang Q
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China. Electronic address: 
      wangqinwen@nbu.edu.cn.
FAU - Wang, C
AU  - Wang C
AD  - Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang 
      Provincial Key Laboratory of Pathophysiology in Ningbo University School of 
      Medicine, Ningbo, Zhejiang 315211, PR China. Electronic address: 
      wangchuang@nbu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140113
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - I89Y79062L (Etazolate)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/*metabolism
MH  - Depression/chemically induced/*drug therapy/*enzymology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Etazolate/*therapeutic use
MH  - Hippocampus/drug effects/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Phosphodiesterase Inhibitors/*therapeutic use
MH  - Prefrontal Cortex/drug effects/metabolism
OTO - NOTNLM
OT  - cyclic adenosine monophosphate (cAMP)
OT  - depression
OT  - etazolate
OT  - interleukin-1beta (IL-1beta)
OT  - lipopolysaccharide (LPS)
OT  - phosphodiesterase-4 (PDE4)
EDAT- 2014/01/18 06:00
MHDA- 2014/11/02 06:00
CRDT- 2014/01/18 06:00
PHST- 2013/10/19 00:00 [received]
PHST- 2014/01/05 00:00 [revised]
PHST- 2014/01/06 00:00 [accepted]
PHST- 2014/01/18 06:00 [entrez]
PHST- 2014/01/18 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
AID - S0306-4522(14)00012-8 [pii]
AID - 10.1016/j.neuroscience.2014.01.008 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Mar 28;263:1-14. doi: 10.1016/j.neuroscience.2014.01.008. Epub 
      2014 Jan 13.