PMID- 24595240
OWN - NLM
STAT- MEDLINE
DCOM- 20150213
LR  - 20211021
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 15
IP  - 3
DP  - 2014 Mar 3
TI  - Inhibition of acetylcholinesterase modulates NMDA receptor antagonist mediated 
      alterations in the developing brain.
PG  - 3784-98
LID - 10.3390/ijms15033784 [doi]
AB  - Exposure to N-methyl-d-aspartate (NMDA) receptor antagonists has been 
      demonstrated to induce neurodegeneration in newborn rats. However, in clinical 
      practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot 
      always be avoided. The present study investigated the effect of the indirect 
      cholinergic agonist physostigmine on neurotrophin expression and the 
      extracellular matrix during NMDA receptor antagonist induced injury to the 
      immature rat brain. The aim was to investigate matrix metalloproteinase (MMP)-2 
      activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP)-2 
      and brain-derived neurotrophic factor (BDNF) after co-administration of the 
      non-competitive NMDA receptor antagonist MK801 (dizocilpine) and the 
      acetylcholinesterase (AChE) inhibitor physostigmine. The AChE inhibitor 
      physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein 
      levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 
      mRNA expression. Our results indicate that AChE inhibition may prevent newborn 
      rats from MK801-mediated brain damage by enhancing neurotrophin-associated 
      signaling pathways and by modulating the extracellular matrix.
FAU - Bendix, Ivo
AU  - Bendix I
AD  - Department of Pediatrics I, Neonatology, University Hospital Essen, Essen 45122, 
      Germany. ivo.bendix@uk-essen.de.
FAU - Serdar, Meray
AU  - Serdar M
AD  - Department of Pediatrics I, Neonatology, University Hospital Essen, Essen 45122, 
      Germany. meray.serdar@uk-essen.de.
FAU - Herz, Josephine
AU  - Herz J
AD  - Department of Pediatrics I, Neonatology, University Hospital Essen, Essen 45122, 
      Germany. josephine.herz@uk-essen.de.
FAU - von Haefen, Clarissa
AU  - von Haefen C
AD  - Department of Anesthesiology and Intensive Care Medicine, 
      Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, 
      Germany. clarissa.von-haefen@charite.de.
FAU - Nasser, Fatme
AU  - Nasser F
AD  - Department of Anesthesiology and Intensive Care Medicine, 
      Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, 
      Germany. fatme21@hotmail.de.
FAU - Rohrer, Benjamin
AU  - Rohrer B
AD  - Department of Anesthesiology and Intensive Care Medicine, 
      Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, 
      Germany. benjamin.rohrer@charite.de.
FAU - Endesfelder, Stefanie
AU  - Endesfelder S
AD  - Department of Neonatology, Charite-Universitatsmedizin Berlin, Campus 
      Virchow-Klinikum, Berlin 13353, Germany. stefanie.endesfelder@charite.de.
FAU - Felderhoff-Mueser, Ursula
AU  - Felderhoff-Mueser U
AD  - Department of Pediatrics I, Neonatology, University Hospital Essen, Essen 45122, 
      Germany. ursula.felderhoff@uk-essen.de.
FAU - Spies, Claudia D
AU  - Spies CD
AD  - Department of Anesthesiology and Intensive Care Medicine, 
      Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, 
      Germany. claudia.spies@charite.de.
FAU - Sifringer, Marco
AU  - Sifringer M
AD  - Department of Anesthesiology and Intensive Care Medicine, 
      Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin 13353, 
      Germany. marco.sifringer@charite.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140303
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 9U1VM840SP (Physostigmine)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Animals
MH  - Brain/*drug effects/growth & development/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cholinesterase Inhibitors/*pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Gene Expression/drug effects
MH  - Immunoblotting
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Physostigmine/pharmacology
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism
PMC - PMC3975367
EDAT- 2014/03/07 06:00
MHDA- 2015/02/14 06:00
PMCR- 2014/03/01
CRDT- 2014/03/06 06:00
PHST- 2013/12/17 00:00 [received]
PHST- 2014/02/20 00:00 [revised]
PHST- 2014/02/21 00:00 [accepted]
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/02/14 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - ijms15033784 [pii]
AID - ijms-15-03784 [pii]
AID - 10.3390/ijms15033784 [doi]
PST - epublish
SO  - Int J Mol Sci. 2014 Mar 3;15(3):3784-98. doi: 10.3390/ijms15033784.