Alcohol, astroglia, and brain development.
Glial cells constitute one of the most common cell types in the brain. They play critical roles in central nervous system (CNS) development. Recent evidence demonstrates that glial cells are profoundly affected by prenatal alcohol exposure, suggesting that alterations in these cells may participate in CNS abnormalities associated with ethanol-induced teratogenesis. In vivo studies show that prenatal exposure to alcohol hampers myelinogenesis and is associated with neuroglial heterotopias and abnormal astrogliogenesis. Studies using primary cultures of rat cortical astrocytes show that ethanol affects DNA, RNA, and protein synthesis, decreases the number of mitotic cells, alters the content and distribution of several cytoskeletal proteins including the astroglial marker, glial fibrillary acidic protein (GFAP), and the levels of plasma-membrane glycoproteins, reduces the capacity of astrocytes to secrete growth factors, and induces oxidative stress. Furthermore, ethanol exposure during early embryogenesis alters the normal development of radial glia cells (the main astrocytic precursors), delays the onset of GFAP expression, and decreases mRNA GFAP levels in fetal and postnatal brains and in radial glia and astrocytes in primary culture. Recent evidence suggests that ethanol interferes with the transcription process of GFAP, thus leading to a reduction in GFAP-gene expression during astrogliogenesis. However, brief exposure of rats to high levels of ethanol during the neonatal period (the period of astrocyte differentiation) causes a transient gliosis, with an increase in GFAP and its mRNA levels. These findings indicate that astroglial cells are an important target of ethanol toxicity during central nervous system (CNS) development.
Guerri
C
C
Instituto Investigaciones Citológicas (FVIB), Amadeo de Saboya, Valencia.
Renau-Piqueras
J
J
D000375:Aging; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005314:Embryonic and Fetal Development; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006801:Humans; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats
D005904:Glial Fibrillary Acidic Protein; D000431:Ethanol