PMID- 28935920
OWN - NLM
STAT- MEDLINE
DCOM- 20190627
LR  - 20190627
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Sep 21
TI  - Inhibition of PDE2 reverses beta amyloid induced memory impairment through 
      regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways.
PG  - 12044
LID - 10.1038/s41598-017-08070-2 [doi]
LID - 12044
AB  - Beta amyloid peptides (Abeta) are known risk factors involved in cognitive 
      impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease 
      (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP 
      and/or cGMP activities, which may ameliorate cognitive deficits associated with 
      AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and 
      neuroinflammatory events, as well as cognitive performance in AD are related to 
      cAMP/cGMP-dependent pathways. The present study investigated how the selective 
      PDE2 inhibitor BAY60-7550 (BAY) affected Abeta-induced learning and memory 
      impairment in two classic rodent models. IL-22 and IL-17, Bax and Bcl-2, PKA/PKG 
      and the brain derived neurotropic factor (BDNF) levels in hippocampus and cortex 
      were detected with immunoblotting assay. The results showed that BAY reversed 
      Abeta-induced cognitive impairment as shown in the water maze test and step-down 
      test. Moreover, BAY treatment reversed the Abeta-induced changes in IL-22 and IL-17 
      and the ratio of Bax/Bcl-2. Changes in cAMP/cGMP levels, PKA/PKG and BDNF 
      expression were also prevented by BAY. These effects of BAY on memory performance 
      and related neurochemical changes were partially blocked by the PKG inhibitor KT 
      5823. These findings indicated that the protective effects of BAY against 
      Abeta-induced memory deficits might involve the regulation of neuroinflammation and 
      neuronal apoptotic events.
FAU - Wang, Li
AU  - Wang L
AD  - Clinical Laboratory, Xuzhou No. 1 People's Hospital, Xuzhou, Jiangsu Province, 
      221002, China.
FAU - Xiaokaiti, Yilixiati
AU  - Xiaokaiti Y
AD  - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical 
      Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
FAU - Wang, Gang
AU  - Wang G
AD  - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing 
      Medical University, Hangzhou, Zhejiang Province, 310006, China.
FAU - Xu, Xiaoxiao
AU  - Xu X
AD  - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 
      Zhejiang Province, 325021, China.
FAU - Chen, Ling
AU  - Chen L
AD  - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing 
      Medical University, Hangzhou, Zhejiang Province, 310006, China.
FAU - Huang, Xianfeng
AU  - Huang X
AD  - School of Pharmaceutical Engineering & Life Sciences, Changzhou University, 
      Changzhou, Jiangsu Province, 213164, China.
FAU - Liu, Li
AU  - Liu L
AD  - School of Pharmaceutical Engineering & Life Sciences, Changzhou University, 
      Changzhou, Jiangsu Province, 213164, China.
FAU - Pan, Jianchun
AU  - Pan J
AD  - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 
      Zhejiang Province, 325021, China.
FAU - Hu, Shuqun
AU  - Hu S
AD  - Xuzhou Medical University, Xuzhou, Jiangsu Province, 221006, China.
FAU - Chen, Zhuoyou
AU  - Chen Z
AD  - Changzhou No. 2 People's Hospital, the Affiliated Hospital of Nanjing Medical 
      University, Changzhou, Jiangsu Province, 213161, China. neuro1972@163.com.
FAU - Xu, Ying
AU  - Xu Y
AD  - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical 
      Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA. 
      yxu9@buffalo.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170921
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 
      (2-(3,4-dimethoxybenzyl)-7-(1-(1-hydroxyethyl)-4-phenylbutyl)-5-methylimidazo(5,1-f)(1,2,4)triazin-4 
      (3H)-one)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Imidazoles)
RN  - 0 (Triazines)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 2)
SB  - IM
MH  - *Alzheimer Disease/drug therapy/enzymology/pathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 2/*antagonists & inhibitors
MH  - Disease Models, Animal
MH  - Imidazoles/*pharmacology
MH  - Learning/drug effects
MH  - Male
MH  - *Memory Disorders/drug therapy/enzymology/pathology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Signal Transduction/drug effects
MH  - Triazines/*pharmacology
PMC - PMC5608906
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/25 06:00
MHDA- 2019/06/30 06:00
PMCR- 2017/09/21
CRDT- 2017/09/23 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/09/23 06:00 [entrez]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2017/09/21 00:00 [pmc-release]
AID - 10.1038/s41598-017-08070-2 [pii]
AID - 8070 [pii]
AID - 10.1038/s41598-017-08070-2 [doi]
PST - epublish
SO  - Sci Rep. 2017 Sep 21;7(1):12044. doi: 10.1038/s41598-017-08070-2.