Cell surface expression of NR1 splice variants and NR2 subunits is modified by prenatal ethanol exposure.
N-methyl-D-aspartate receptor dysfunction has been strongly suggested to link with the abnormalities seen in fetal alcohol syndrome. Thus, the effects of prenatal ethanol exposure on the total expression of NR1 splice variants and the cell surface expression of both NR1 and NR2 subunits in brain were investigated in rats. Western blot studies of membrane homogenates from cerebral cortices at postnatal days 1 through 21 indicate that prenatal ethanol treatment does not alter total NR1 expression or differential expression of NR1 splice variants during development. However, immunoprecipitation studies using PSD95 suggest that both C2'-terminal variants and NR2A subunits at the cortical postsynaptic membrane of postnatal day 21 were significantly reduced after prenatal ethanol treatment. Moreover, C1-terminal variants were decreased in both pair-fed and ethanol-treated groups, while no significant differences in the levels of total NR1 subunits, NR1 splice variants containing the N- or C2-terminal cassettes, or NR2B subunits were observed. Thus, these results suggest that prenatal exposure to ethanol may influence neuronal function by selective regulation of expression of C2'-terminal variants and NR2A subunits at the cell surface.
Honse
Y
Y
Division of Pharmacology and Toxicology, College of Pharmacy and Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA. yhonse@mail.nih.gov
Nixon
K M
KM
Browning
M D
MD
Leslie
S W
SW
D000375:Aging; D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D000431:Ethanol