PMID- 22467667
OWN - NLM
STAT- MEDLINE
DCOM- 20130923
LR  - 20161125
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Linking)
VI  - 23
IP  - 4
DP  - 2013 Apr
TI  - Phencyclidine-induced decrease of synaptic connectivity via inhibition of BDNF 
      secretion in cultured cortical neurons.
PG  - 847-58
LID - 10.1093/cercor/bhs074 [doi]
AB  - Repeated administration of phencyclidine (PCP), a noncompetitive 
      N-methyl-D-aspartate (NMDA) receptor blocker, produces schizophrenia-like 
      behaviors in humans and rodents. Although impairment of synaptic function has 
      been implicated in the effect of PCP, the molecular mechanisms have not yet been 
      elucidated. Considering that brain-derived neurotrophic factor (BDNF) plays an 
      important role in synaptic plasticity, we examined whether exposure to PCP leads 
      to impaired BDNF function in cultured cortical neurons. We found that PCP caused 
      a transient increase in the level of intracellular BDNF within 3 h. Despite the 
      increased intracellular amount of BDNF, activation of Trk receptors and 
      downstream signaling cascades, including MAPK/ERK1/2 and PI3K/Akt pathways, were 
      decreased. The number of synaptic sites and expression of synaptic proteins were 
      decreased 48 h after PCP application without any impact on cell viability. Both 
      electrophysiological and biochemical analyses revealed that PCP diminished 
      glutamatergic neurotransmission. Furthermore, we found that the secretion of BDNF 
      from cortical neurons was suppressed by PCP. We also confirmed that PCP-caused 
      downregulation of Trk signalings and synaptic proteins were restored by exogenous 
      BDNF application. It is possible that impaired secretion of BDNF and subsequent 
      decreases in Trk signaling are responsible for the loss of synaptic connections 
      caused by PCP.
FAU - Adachi, Naoki
AU  - Adachi N
AD  - Department of Mental Disorder Research, National Institute of Neuroscience, 
      National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
FAU - Numakawa, Tadahiro
AU  - Numakawa T
FAU - Kumamaru, Emi
AU  - Kumamaru E
FAU - Itami, Chiaki
AU  - Itami C
FAU - Chiba, Shuichi
AU  - Chiba S
FAU - Iijima, Yoshimi
AU  - Iijima Y
FAU - Richards, Misty
AU  - Richards M
FAU - Katoh-Semba, Ritsuko
AU  - Katoh-Semba R
FAU - Kunugi, Hiroshi
AU  - Kunugi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120330
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EUY85H477I (thiazolyl blue)
RN  - J1DOI7UV76 (Phencyclidine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Biophysics
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Nerve Tissue Proteins/metabolism
MH  - *Neurons/cytology/drug effects/metabolism
MH  - Neurotransmitter Agents/metabolism
MH  - Patch-Clamp Techniques
MH  - Phencyclidine/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Receptors, Glutamate/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Synapses/*drug effects
MH  - Synaptic Potentials/drug effects
MH  - Tetrazolium Salts/metabolism
MH  - Thiazoles/metabolism
MH  - Time Factors
EDAT- 2012/04/03 06:00
MHDA- 2013/09/24 06:00
CRDT- 2012/04/03 06:00
PHST- 2012/04/03 06:00 [entrez]
PHST- 2012/04/03 06:00 [pubmed]
PHST- 2013/09/24 06:00 [medline]
AID - bhs074 [pii]
AID - 10.1093/cercor/bhs074 [doi]
PST - ppublish
SO  - Cereb Cortex. 2013 Apr;23(4):847-58. doi: 10.1093/cercor/bhs074. Epub 2012 Mar 
      30.