PMID- 28415673
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20181202
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 22
DP  - 2017 May 30
TI  - cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 
      2-induced learning/memory deficits of rats subjected to chronic unpredictable 
      mild stress.
PG  - 35558-35572
LID - 10.18632/oncotarget.16009 [doi]
AB  - To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory 
      impairments in rats subjected to chronic unpredictable mild stress (CUMS), 
      meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. 
      Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was 
      injected intraventricularly to increase or decrease the enzyme's expression, 
      respectively. The body weights and sucrose consumption were used to analyze 
      depressive behaviors, while the Morris water maze and step-down-type passive 
      avoidance tests were carried out to evaluate the learning-memory functions. The 
      levels of inflammatory cytokines were measured to estimate inflammation and the 
      contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels 
      of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed 
      using reverse transcription polymerase chain reaction. Moreover, the expression 
      of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins 
      receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein 
      (CREB), and phosphorylated CREB were estimated using immunohistochemical staining 
      or western blotting. The results showed that CUMS led to significant 
      depressive-like behaviors and learning and memory dysfunctions. Also, the cAMP 
      levels decreased significantly, while levels of inflammatory cytokines and 
      prostaglandins E2 increased significantly. The expressions of PKA, BDNF, 
      phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam 
      and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS 
      while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities. 
      The findings also showed that CUMS increased cyclooxygenase 2 expression, which 
      can cause learning and memory impairments, mainly through activating the 
      hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.
FAU - Luo, Ying
AU  - Luo Y
AD  - Department of Pharmacology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 
      China.
FAU - Kuang, Shengnan
AU  - Kuang S
AD  - Department of Pharmacology, Chongqing Medical University, Chongqing, China.
AD  - Department of Pharmacy, People's Hospital of Rongchang, Chongqing, China.
FAU - Li, Huan
AU  - Li H
AD  - Department of Pharmacology, Chongqing Medical University, Chongqing, China.
FAU - Ran, Dongzhi
AU  - Ran D
AD  - Department of Pharmacology, Chongqing Medical University, Chongqing, China.
FAU - Yang, Junqing
AU  - Yang J
AD  - Department of Pharmacology, Chongqing Medical University, Chongqing, China.
AD  - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 
      China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Thiazines)
RN  - 0 (Thiazoles)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - VG2QF83CGL (Meloxicam)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/pharmacology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Learning/drug effects
MH  - Meloxicam
MH  - Memory/drug effects
MH  - Memory Disorders/drug therapy/etiology/metabolism/physiopathology
MH  - Rats
MH  - *Signal Transduction
MH  - Stress, Psychological
MH  - Synapses/drug effects/metabolism
MH  - Thiazines/pharmacology
MH  - Thiazoles/pharmacology
PMC - PMC5482598
OTO - NOTNLM
OT  - BDNF
OT  - Neuroscience
OT  - cognitive impairment
OT  - cyclooxygenase2
OT  - hippocampus
OT  - inflammation
COIS- CONFLICTS OF INTERESTS The authors declare no competing financial interests.
EDAT- 2017/04/19 06:00
MHDA- 2018/03/27 06:00
PMCR- 2017/05/30
CRDT- 2017/04/19 06:00
PHST- 2017/01/19 00:00 [received]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/05/30 00:00 [pmc-release]
AID - 16009 [pii]
AID - 10.18632/oncotarget.16009 [doi]
PST - ppublish
SO  - Oncotarget. 2017 May 30;8(22):35558-35572. doi: 10.18632/oncotarget.16009.