Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins.
The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chlorophenylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q1b and D3, was a slower rise in M1 and D1a. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by (3H) sialic acid released by Neuraminidase from periodate-(3H)borohydride labeled glycoproteins, have mobilities of the cell adhesion molecules N-CAM and D-CAM. Whether the reduction of the sialoglycoproteins induced by maternal PKU is mainly in these cell adhesion molecules requires further investigation. Interference with the function of gangliosides and certain sialoglycoproteins during cerebral development may contribute to the brain dysfunction observed in the offspring of PKU mothers not on diet control during pregnancy.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002850:Chromatography, Gel; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010661:Phenylketonurias / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012795:Sialoglycoproteins / Q000378:metabolism*
D005732:Gangliosides; D009419:Nerve Tissue Proteins; D012795:Sialoglycoproteins; D004247:DNA; D002784:Cholesterol