Document Detail

Methylnitrosourea induces neural progenitor cell apoptosis and microcephaly in mouse embryos.
MedLine Citation:
PMID:  20549696     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Prenatal exposure to methylnitrosourea (MNU), an alkylating agent, induces microcephaly in mice. However, its pathogenetic mechanism has not been clarified, especially that in the development of the cerebral cortex. METHODS: ICR mice were treated with MNU at 10 mg/kg intraperitoneally on day 13.5 or 15.5 of gestation, and the embryos were observed histologically 24 hr after treatment with MNU or at term. To clarify the pathogenesis of microcephaly and histological changes, especially apoptosis, neurogenesis, and neural migration/positioning, we performed histological analysis employing a cell-specific labeling experiment using thymidine-like substances (BrdU, CldU, and IdU) and markers of neurons/neural stem cells. RESULTS: Histological abnormalities of the dorsal telencephalon, and the excessive cell death of proliferative neural progenitor/stem cells were noted in the MNU-treated embryos. The highest frequencies of cell death occurred at 36 hr after MNU treatment, and little or no neurogenesis was observed in the ventricular zone of the dorsal telencephalon. Abnormality of the radial migration was caused by the reduction of radial fibers in the radial glias. Birth-date analysis revealed the abnormal positioning of neurons and aberrant lamination of the cerebral cortex. CONCLUSIONS: Our data suggest that prenatal exposure to MNU induces the excessive cell death of neural precursor/stem cells, and the defective development of the cerebral cortex, resulting in microcephalic abnormalities.
Munekazu Komada; Fusako Fujiyama; Shigehito Yamada; Kohei Shiota; Tetsuji Nagao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Birth defects research. Part B, Developmental and reproductive toxicology     Volume:  89     ISSN:  1542-9741     ISO Abbreviation:  Birth Defects Res. B Dev. Reprod. Toxicol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155115     Medline TA:  Birth Defects Res B Dev Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  213-22     Citation Subset:  IM    
Congenital Anomaly Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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MeSH Terms
Apoptosis / drug effects*
Body Weight / drug effects
Brain / abnormalities,  drug effects,  embryology
Cell Count
Cell Differentiation / drug effects
Cell Movement / drug effects
Embryo, Mammalian / abnormalities*,  drug effects,  pathology
Methylnitrosourea / toxicity*
Mice, Inbred ICR
Microcephaly / chemically induced*,  embryology*
Neurons / drug effects,  pathology*
Organ Size / drug effects
Stem Cells / drug effects,  pathology*
Telencephalon / drug effects,  embryology,  pathology
Reg. No./Substance:

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