PMID- 28240721
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20180112
IS  - 1473-558X (Electronic)
IS  - 0959-4965 (Linking)
VI  - 28
IP  - 5
DP  - 2017 Mar 22
TI  - Cucurbitacin IIa exerts antidepressant-like effects on mice exposed to chronic 
      unpredictable mild stress.
PG  - 259-267
LID - 10.1097/WNR.0000000000000747 [doi]
AB  - Cucurbitacin IIa (CuIIa) is the major active component of the Helmseya amabilis 
      root and is known to have antiviral and anti-inflammatory effects. In this study, 
      we examined the antidepressant-like effects of CuIIa in a mouse model of chronic 
      unpredictable mild stress (CUMS) and investigated the possible underlying 
      mechanisms. To evaluate the antidepressant-like effects of CuIIa on 
      depression-like behaviors, mice were subjected to the open-field test, the 
      elevated plus-maze test, the forced-swimming test, and the tail-suspension test. 
      We found that CuIIa treatment reversed the CUMS-induced behavioral abnormalities. 
      Western blot analyses showed that CUMS significantly decreased brain-derived 
      neurotrophic factor (BDNF) levels, cAMP-response element binding protein (CREB), 
      and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation, and 
      N-methyl-D-aspartate receptor subtype GluN2B and 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 expression in 
      the amygdala; in addition, the expression of gamma-aminobutyric acid receptor A 
      subunit alpha2 was upregulated in CUMS mice. These CUMS-induced changes were all 
      normalized by CuIIa treatment and administration of the BDNF antagonist ANA-12 
      can block the antidepressant effect of CuIIa. Our findings suggest that the 
      antidepressant-like effects of CuIIa may be exerted by regulation of the 
      CaMKIIalpha-CREB-BDNF pathway and the balance between excitatory and inhibitory 
      synaptic transmission in the amygdala.
FAU - Zhou, Shi-Meng
AU  - Zhou SM
AD  - Departments of aPharmacology bMedicinal Chemistry cPharmaceutical Analysis, 
      School of Pharmacy dClinical medicine Cadet Brigade, Fourth Military Medical 
      University, Xi'an, China.
FAU - Guan, Shao-Yu
AU  - Guan SY
FAU - Yang, Le
AU  - Yang L
FAU - Yang, Liu-Kun
AU  - Yang LK
FAU - Wang, Lu
AU  - Wang L
FAU - Nie, Hui-Fang
AU  - Nie HF
FAU - Li, Xiang
AU  - Li X
FAU - Zhao, Ming-Gao
AU  - Zhao MG
FAU - Yang, Qi
AU  - Yang Q
FAU - Wu, Hong
AU  - Wu H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (ANA 12 compound)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Azepines)
RN  - 0 (Benzamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (cucurbitacin IIa)
RN  - 60137-06-6 (Cucurbitacins)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Amygdala/drug effects/metabolism
MH  - Animals
MH  - Antidepressive Agents/*therapeutic use
MH  - Azepines/therapeutic use
MH  - Benzamides/therapeutic use
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - CREB-Binding Protein/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Chronic Disease
MH  - Cucurbitacins/*therapeutic use
MH  - Depression/*drug therapy/*etiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Exploratory Behavior/drug effects
MH  - Hindlimb Suspension
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Stress, Psychological/*complications/drug therapy
MH  - Swimming/psychology
EDAT- 2017/02/28 06:00
MHDA- 2018/01/13 06:00
CRDT- 2017/02/28 06:00
PHST- 2017/02/28 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2017/02/28 06:00 [entrez]
AID - 10.1097/WNR.0000000000000747 [doi]
PST - ppublish
SO  - Neuroreport. 2017 Mar 22;28(5):259-267. doi: 10.1097/WNR.0000000000000747.