PMID- 11696674
OWN - NLM
STAT- MEDLINE
DCOM- 20020207
LR  - 20131121
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 25
IP  - 10
DP  - 2001 Oct
TI  - Selective vulnerability of embryonic cell populations to ethanol-induced 
      apoptosis: implications for alcohol-related birth defects and neurodevelopmental 
      disorder.
PG  - 1523-35
AB  - BACKGROUND: Ethanol-induced cell death has been characterized in very few stages 
      of embryogenesis. This investigation comprehensively maps patterns of both 
      programmed and ethanol-induced cell death in the central nervous system and 
      craniofacial region at 0.5-day intervals from gestational day (GD) 6.5 to 11 in 
      mice. METHODS: A teratogenic dosage of ethanol (2.9 g/kg) or vehicle was 
      administered via two intraperitoneal injections to pregnant C57BL/6J mice at 
      various stages of gestation. Cell death patterns were characterized using Nile 
      blue sulfate vital staining and histological analysis of plastic sections. 
      Confocal laser scanning microscopy of LysoTracker Red-stained specimens allowed 
      for three-dimensional visualization of areas of apoptosis and precise sectional 
      imaging of mouse embryos. Apoptosis was also documented using a TUNEL technique 
      on histological sections. RESULTS: Normal programmed cell death in control 
      embryos was noted in the prechordal plate region at GD 8, the neuroepithelium of 
      the fourth ventricle and anterior neuropore at GD 9, and within the ganglia of 
      cranial nerves V, VII-VIII, IX, and X at GD 10. Acute maternal ethanol 
      administration 12 hr before examination resulted in a dramatic increase in 
      apoptosis within sites of programmed cell death in the embryo. Moreover, 
      ethanol-exposed specimens exhibited stage-dependent excessive cell death in other 
      distinct cell populations, particularly within the developing central nervous 
      system. Ethanol-induced apoptosis was notable as follows: GD 7.5-neuroectoderm; 
      GD 8-neural plate and primitive streak; GD 9-alar plate and presumptive neural 
      crest of the rostral hindbrain, especially at the mesencephalon/rhombencephalon 
      junction; GD 9.5-10-branchial arches and rhombomeres; and GD 11-diencephalon, 
      basal ganglia, pons, and developing cerebellum. CONCLUSIONS: The results of this 
      study revealed developmental stage-specific cell populations of the developing 
      brain and craniofacial region that are vulnerable to ethanol-induced apoptosis 
      and provide new insight relative to the genesis of alcohol-related birth defects.
FAU - Dunty, W C Jr
AU  - Dunty WC Jr
AD  - Department of Cell and Developmental Biology and the Bowles Center for Alcohol 
      Studies, University of North Carolina at Chapel Hill, 27599-7090, USA.
FAU - Chen, S Y
AU  - Chen SY
FAU - Zucker, R M
AU  - Zucker RM
FAU - Dehart, D B
AU  - Dehart DB
FAU - Sulik, K K
AU  - Sulik KK
LA  - eng
GR  - AA11605/AA/NIAAA NIH HHS/United States
GR  - DA-07244/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Central Nervous System/*embryology/pathology
MH  - Embryo, Mammalian/drug effects/pathology/physiology
MH  - Ethanol/*pharmacology
MH  - Face/*embryology
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/embryology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nervous System Diseases/chemically induced/embryology
MH  - Pregnancy
MH  - Skull/*embryology
EDAT- 2001/11/07 10:00
MHDA- 2002/02/08 10:01
CRDT- 2001/11/07 10:00
PHST- 2001/11/07 10:00 [pubmed]
PHST- 2002/02/08 10:01 [medline]
PHST- 2001/11/07 10:00 [entrez]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2001 Oct;25(10):1523-35.