PMID- 24776773
OWN - NLM
STAT- MEDLINE
DCOM- 20150226
LR  - 20171116
IS  - 1423-0224 (Electronic)
IS  - 0302-282X (Linking)
VI  - 69
IP  - 3
DP  - 2014
TI  - Antidepressant and neuroprotective effect of the Chinese herb kaixinsan against 
      lentiviral shRNA knockdown brain-derived neurotrophic factor-induced injury in 
      vitro and in vivo.
PG  - 129-39
LID - 10.1159/000358089 [doi]
AB  - Depression has been associated with reduced expression of brain-derived 
      neurotrophic factor (BDNF) in the hippocampus. Previous studies have demonstrated 
      that the herbal medicine formula, 'kaixinsan' (KXS), could ameliorate the 
      severity of depression and increase cAMP response element-binding protein 
      expression. There is direct evidence suggesting that the reduction of the BDNF 
      protein in specific brain sites can provoke depressive-like behaviour or affect 
      neurogenesis in vivo. However, the biological mechanisms between the 
      antidepressant and neuroprotective effect of KXS and the alterations in BDNF 
      levels in in vivo and in vitro models remain unclear. Using BDNF knockdown 
      mediated by lentiviral vectors (LV-shBDNF-3) transfected with primary hippocampal 
      neurons and following injection into the dentate gyrus of the hippocampus, it was 
      demonstrated that a reduction in BDNF expression affects cell viability and 
      animal behaviours associated with depression. During treatment with KXS after the 
      lentiviral shRNA silencing of BDNF in cell and animal, cell viability, body 
      weight, the sucrose preference test (SPT), the open field test (OFT) the Morris 
      Water Maze (MWM) task and BDNF expression were measured. KXS attenuated 
      LV-shBDNF-3-induced cell death in primary hippocampal neurons and also improved 
      the sucrose intake in SPT, ambulatory response in OFT and learning ability in MWM 
      against LV-shBDNF-3-induced depressive-like syndromes. Moreover, immunoblot 
      analysis confirmed that KXS could reverse LV-shBDNF-induced BDNF reduction either 
      in vitro or in vivo. These findings provide substantial evidence for supporting a 
      neurotrophic hypothesis of depression and specify BDNF targets for potential 
      antidepressant interventions. Moreover, the antagonism between LV-shRNA BDNF 
      knockdown and KXS may depend on multiple compounds with synergistic mechanisms 
      that modulate the different signal transduction networks directly or indirectly, 
      increasing BDNF expression and exerting its neuroprotective and 
      antidepressant-like effects.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Hu, Yuan
AU  - Hu Y
AD  - Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, 
      China.
FAU - Zhou, Xiao-Jiang
AU  - Zhou XJ
FAU - Liu, Ping
AU  - Liu P
FAU - Dong, Xian-Zhe
AU  - Dong XZ
FAU - Mu, Li-Hua
AU  - Mu LH
FAU - Chen, Yi-Bang
AU  - Chen YB
FAU - Liu, Ming-Yue
AU  - Liu MY
FAU - Yu, Bing-Ying
AU  - Yu BY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140426
PL  - Switzerland
TA  - Neuropsychobiology
JT  - Neuropsychobiology
JID - 7512895
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Kai-Xin-San)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Body Weight/drug effects
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cell Line
MH  - Cell Survival/*drug effects
MH  - Depression/drug therapy
MH  - Drugs, Chinese Herbal/*pharmacology/therapeutic use
MH  - Food Preferences/drug effects
MH  - Gene Knockdown Techniques
MH  - Genetic Vectors/genetics
MH  - Hippocampus/drug effects/metabolism
MH  - In Vitro Techniques
MH  - Lentivirus/genetics
MH  - Maze Learning/drug effects
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Primary Cell Culture
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
EDAT- 2014/04/30 06:00
MHDA- 2015/02/27 06:00
CRDT- 2014/04/30 06:00
PHST- 2013/03/14 00:00 [received]
PHST- 2013/12/16 00:00 [accepted]
PHST- 2014/04/30 06:00 [entrez]
PHST- 2014/04/30 06:00 [pubmed]
PHST- 2015/02/27 06:00 [medline]
AID - 000358089 [pii]
AID - 10.1159/000358089 [doi]
PST - ppublish
SO  - Neuropsychobiology. 2014;69(3):129-39. doi: 10.1159/000358089. Epub 2014 Apr 26.