Differential display identifies neuroendocrine-specific protein-A (NSP-A) and interferon-inducible protein 10 (IP-10) as ethanol-responsive genes in the fetal rat brain.
Fetal alcohol exposure is the most common nonhereditary cause of mental retardation in the western world. Rats prenatally treated with ethanol liquid diet exhibit extensive defects in the brain that accurately model those observed in humans. To analyze the ethanol effects on gene expression during brain development, we performed mRNA differential display and two-dimensional electrophoresis on gestational day (G) 13 and G 16 brain from rats treated with ethanol liquid diet. Using mRNA differential display followed by a variety of quantitative analyses, three genes were confirmed to be ethanol-responsive. Among them was Neuroendocrine-Specific Protein-A (NSP-A), which is known to be affected by thyroid hormone in the cortex at this developmental time. However, two additional genes known to be thyroid hormone-responsive were unaffected by ethanol, indicating that interference with thyroid hormone action may not be a predominant pathway by which alcohol induces damage in the fetal brain. The observation that interferon-inducible protein-10 (IP-10) is up-regulated in ethanol-treated fetal brain may indicate the presence of a disease process recruiting CD8+ T-cells capable of interfering with myelination. The result of two-dimensional (2D) electrophoresis and Western analyses demonstrated that few changes in the abundance of individual proteins or the phosphorylation of proteins at threonine and tyrosine were induced by prenatal ethanol exposure. A critical analysis of the approaches used in the present study may be important for future studies in this field.
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology* / Q000201:enzymology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D013205:Staphylococcal Protein A / Q000096:biosynthesis / Q000235:genetics
D002492:Central Nervous System Depressants; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C489913:Rtn1 protein, rat; D013205:Staphylococcal Protein A; D000431:Ethanol