PMID- 26562663
OWN - NLM
STAT- MEDLINE
DCOM- 20160919
LR  - 20151218
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1630
DP  - 2016 Jan 1
TI  - Activation of hippocampal BDNF signaling is involved in the antidepressant-like 
      effect of the NMDA receptor antagonist 7-chlorokynurenic acid.
PG  - 73-82
LID - S0006-8993(15)00848-3 [pii]
LID - 10.1016/j.brainres.2015.11.005 [doi]
AB  - Previous studies showed that acute 7-chlorokynurenic acid treatment produced a 
      rapid antidepressant-like action in depression-like animal models. However, the 
      underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid 
      is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic 
      acid treatment produced an antidepressant-like effect through the activation of 
      brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic 
      unpredictable mild stress (CUMS). In addition, we performed an oral toxicological 
      evaluation of chronic 7-chlorokynurenic acid administration in mice. The results 
      showed that a two-week administration with 7-chlorokynurenic acid reversed the 
      decreased sucrose preference and prolonged first feeding latency. In addition, 
      7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of 
      BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. 
      In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase 
      receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 
      7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not 
      produce any toxicological effect in mice. In conclusion, our findings suggest 
      that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at 
      least in part, by activating BDNF signaling in the hippocampus.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Li, Cheng-Fu
AU  - Li CF
AD  - Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361009, Fujian Province, 
      PR China. Electronic address: lichengfu103@126.com.
FAU - Chen, Xue-Mei
AU  - Chen XM
AD  - Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361009, Fujian Province, 
      PR China.
FAU - Chen, Shao-Mei
AU  - Chen SM
AD  - Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361009, Fujian Province, 
      PR China.
FAU - Mu, Rong-Hao
AU  - Mu RH
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China.
FAU - Liu, Bin-Bin
AU  - Liu BB
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China.
FAU - Luo, Liu
AU  - Luo L
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China.
FAU - Liu, Xiao-Long
AU  - Liu XL
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China.
FAU - Geng, Di
AU  - Geng D
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, 
      Huaqiao University, Xiamen 361021, Fujian Province, PR China.
FAU - Liu, Qing
AU  - Liu Q
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, 
      Huaqiao University, Xiamen 361021, Fujian Province, PR China.
FAU - Yi, Li-Tao
AU  - Yi LT
AD  - Department of Chemical and Pharmaceutical Engineering, Huaqiao University, Xiamen 
      361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, 
      Huaqiao University, Xiamen 361021, Fujian Province, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151110
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - H030S2S85J (Kynurenic Acid)
RN  - S7936QON2K (7-chlorokynurenic acid)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/toxicity
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Depressive Disorder/*drug therapy/metabolism
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Hippocampus/*drug effects/metabolism/pathology
MH  - Kidney/drug effects/pathology
MH  - Kynurenic Acid/*analogs & derivatives/pharmacology/toxicity
MH  - Liver/drug effects/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Mice, Inbred ICR
MH  - Random Allocation
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - Stress, Psychological/drug therapy/metabolism
MH  - Uncertainty
OTO - NOTNLM
OT  - 7-Chlorokynurenic acid
OT  - Brain-derived neurotrophic factor
OT  - Depression
OT  - Toxicological evaluation
EDAT- 2015/11/13 06:00
MHDA- 2016/09/20 06:00
CRDT- 2015/11/13 06:00
PHST- 2015/08/07 00:00 [received]
PHST- 2015/10/28 00:00 [revised]
PHST- 2015/11/02 00:00 [accepted]
PHST- 2015/11/13 06:00 [entrez]
PHST- 2015/11/13 06:00 [pubmed]
PHST- 2016/09/20 06:00 [medline]
AID - S0006-8993(15)00848-3 [pii]
AID - 10.1016/j.brainres.2015.11.005 [doi]
PST - ppublish
SO  - Brain Res. 2016 Jan 1;1630:73-82. doi: 10.1016/j.brainres.2015.11.005. Epub 2015 
      Nov 10.