PMID- 11948666
OWN - NLM
STAT- MEDLINE
DCOM- 20020503
LR  - 20131121
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 68
IP  - 2
DP  - 2002 Apr 15
TI  - Ethanol exposure enhances cell death in the developing cerebral cortex: role of 
      brain-derived neurotrophic factor and its signaling pathways.
PG  - 213-25
AB  - Exposure to ethanol during fetal development induces brain damage, causing cell 
      loss in several brain areas and affecting synaptic connections. Because 
      neurotrophin signaling plays an important role in neuronal survival and 
      differentiation, we have investigated the effect of ethanol exposure on cell 
      death in the developing cerebral cortex and whether this effect correlates with 
      alterations in brain-derived neurotrophic factor (BDNF) levels, expression of its 
      receptors, TrkB, and its signaling. We report that chronic ethanol intake during 
      gestation and lactation enhances natural cell death and induces cell necrosis, 
      decreases BDNF levels, and increases the ratio of the truncated to full-length 
      TrkB mRNA receptors during postnatal developing cerebral cortex. Furthermore, we 
      provide evidence that during brain development BDNF activates the extracellular 
      signal-regulated kinases (ERK1 and ERK2) and the phosphoinoside-3-kinase 
      (PI-3-K/Akt) pathways. However, BDNF-induced cell signaling throughout the 
      above-mentioned survival pathways is significantly reduced by ethanol exposure. 
      These findings suggest that ethanol-induced alterations in BDNF availability and 
      in its receptor function might impair intracellular signaling pathways involved 
      in cell survival, growth, and differentiation, leading to enhanced natural cell 
      death during cerebral cortex development.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Climent, E
AU  - Climent E
AD  - Instituto de Investigaciones Citologicas (FVIB), Amadeo de Saboya 4, 
      46010-Valencia, Spain.
FAU - Pascual, M
AU  - Pascual M
FAU - Renau-Piqueras, J
AU  - Renau-Piqueras J
FAU - Guerri, Consuelo
AU  - Guerri C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptide Fragments)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Animals, Newborn/*growth & development
MH  - Apoptosis/drug effects
MH  - Brain/growth & development
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Death/drug effects
MH  - Cerebral Cortex/*drug effects/pathology/*physiology
MH  - Enzyme Activation
MH  - Ethanol/*pharmacology
MH  - Female
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Necrosis
MH  - Peptide Fragments/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/chemistry/metabolism
MH  - Signal Transduction/physiology
EDAT- 2002/04/12 10:00
MHDA- 2002/05/04 10:01
CRDT- 2002/04/12 10:00
PHST- 2002/04/12 10:00 [pubmed]
PHST- 2002/05/04 10:01 [medline]
PHST- 2002/04/12 10:00 [entrez]
AID - 10.1002/jnr.10208 [pii]
AID - 10.1002/jnr.10208 [doi]
PST - ppublish
SO  - J Neurosci Res. 2002 Apr 15;68(2):213-25. doi: 10.1002/jnr.10208.