Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes.
Prenatal ethanol exposure induces functional abnormalities during brain development affecting neurogenesis and gliogenesis. We have previously reported that alcohol exposure during embryogenesis disrupts radial glia (RG) and gliogenesis. Taking into account the new role of RG as neural progenitors, we have investigated whether ethanol affects RG as a neural stem cell. We found that in utero ethanol exposure impairs cell proliferation and decreases neurons and astrocytes generated in cultured RG and in embryonic cerebral cortex. Telencephalic cultures obtained at E12 from ethanol-treated rats displayed a reduction in the proportion of actively dividing RG progenitors, as demonstrated by 5-bromo-2'-deoxyuridine incorporation, and in the percentage of brain lipid binding protein-positive RG. Consistently, neurosphere formation assay from E12 telencephalon showed a reduced number of multipotent progenitor cells in cultures isolated from ethanol-treated rats in comparison with pair-fed control group. Moreover, levels of activated Notch1 and fibroblast growth factor receptor 2, which regulate the maintenance of the progenitor state of RG, are decreased by prenatal ethanol exposure. These findings demonstrate that ethanol reduces the telencephalic RG progenitor pool and its transformation into neurons and astrocytes, which may contribute to an explanation of the defects in brain function often observed in fetal alcohol syndrome.
Rubert
Gemma
G
Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Miñana
Rosa
R
Pascual
Maria
M
Guerri
Consuelo
C
D020268:Alcohol-Induced Disorders, Nervous System / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000002:abnormalities* / Q000187:drug effects* / Q000503:physiopathology; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000009:adverse effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000187:drug effects / Q000378:metabolism; D051881:Receptor, Notch1 / Q000187:drug effects / Q000378:metabolism; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013687:Telencephalon / Q000002:abnormalities / Q000187:drug effects / Q000503:physiopathology
D002492:Central Nervous System Depressants; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D000431:Ethanol; C496356:Fgfr2 protein, rat; D051497:Receptor, Fibroblast Growth Factor, Type 2; D001973:Bromodeoxyuridine