PMID- 24615983
OWN - NLM
STAT- MEDLINE
DCOM- 20141128
LR  - 20161125
IS  - 1098-2396 (Electronic)
IS  - 0887-4476 (Linking)
VI  - 68
IP  - 6
DP  - 2014 Jun
TI  - Phencyclidine rapidly decreases neuronal mRNA of brain-derived neurotrophic 
      factor.
PG  - 257-65
LID - 10.1002/syn.21735 [doi]
AB  - Downregulation of brain-derived neurotrophic factor (BDNF), a member of 
      neurotrophin family, has been implicated in psychiatric diseases including 
      schizophrenia. However, detailed mechanisms of its reduction in patients with 
      schizophrenia remain unclear. Here, using cultured cortical neurons, we monitored 
      BDNF mRNA levels following acute application of phencyclidine [PCP; an 
      N-methyl-d-aspartate (NMDA) receptor blocker], which is known to produce 
      schizophrenia-like symptoms. We found that PCP rapidly caused a reduction in 
      total amount of BDNF transcripts without effect on cell viability, while mRNA 
      levels of nerve growth factor was intact. Actinomycin-D (ActD), an RNA synthesis 
      inhibitor, decreased total BDNF mRNA levels similar to PCP, and coapplication of 
      ActD with PCP did not show further reduction in BDNF mRNA compared with solo 
      application of each drug. Among BDNF exons I, IV, and VI, the exon IV, which is 
      positively regulated by neuronal activity, was highly sensitive to PCP. 
      Furthermore, PCP inactivated cAMP response element-binding protein (CREB; a 
      regulator of transcriptional activity of exon IV). The inactivation of CREB was 
      also achieved by an inhibitor for Ca(2+) /calmodulin kinase II (CaMKII), although 
      coapplication with PCP induced no further inhibition on the CREB activity. It is 
      possible that PCP decreases BDNF transcription via blocking the NMDA 
      receptor/CaMKII/CREB signaling.
CI  - Copyright (c) 2014 Wiley Periodicals, Inc.
FAU - Katanuma, Yusuke
AU  - Katanuma Y
AD  - Department of Mental Disorder Research, National Institute of Neuroscience, 
      National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Life 
      Science and Medical Bioscience, School of Advanced Science and Engineering, 
      Waseda University, Tokyo, Japan.
FAU - Numakawa, Tadahiro
AU  - Numakawa T
FAU - Adachi, Naoki
AU  - Adachi N
FAU - Yamamoto, Noriko
AU  - Yamamoto N
FAU - Ooshima, Yoshiko
AU  - Ooshima Y
FAU - Odaka, Haruki
AU  - Odaka H
FAU - Inoue, Takafumi
AU  - Inoue T
FAU - Kunugi, Hiroshi
AU  - Kunugi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140224
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hallucinogens)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (Crebbp protein, rat)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - CREB-Binding Protein/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Dactinomycin/pharmacology
MH  - Exons
MH  - Hallucinogens/*pharmacology
MH  - Nerve Growth Factor/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Phencyclidine/*pharmacology
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/genetics/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - BDNF
OT  - NMDA receptor
OT  - phencyclidine
OT  - schizophrenia
EDAT- 2014/03/13 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/03/12 06:00
PHST- 2013/09/26 00:00 [received]
PHST- 2014/02/07 00:00 [accepted]
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1002/syn.21735 [doi]
PST - ppublish
SO  - Synapse. 2014 Jun;68(6):257-65. doi: 10.1002/syn.21735. Epub 2014 Feb 24.