Effects of chronic ethanol administration on poly-phosphoinositide metabolism in the mouse brain: variance with age.
Using a procedure in which poly-phosphoinositides (poly-PI) in C57Bl mouse brain were labeled with [32P]Pi or [32P]ATP, the effects of chronic ethanol administration and age on metabolism of these anionic phospholipids were examined. Within 4 h after intracerebral injection, both labeled precursors were effectively incorporated into membrane phospholipids with high proportions of labeling among phosphatidylcholine, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate. With few exceptions, the phospholipid labeling patterns in different brain regions, e.g. cortex, hippocampus and hypothalamus, were similar. However, when the brain homogenate was subjected to differential and sucrose-Ficoll gradient centrifugation, different phospholipid labeling patterns were observed in the subcellular membrane fractions. Young adult mice given an ethanol (5% w/v) liquid diet for 2 months showed an increase in the levels of labeled phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylserine in the cortex and hippocampus as compared to the pair-fed controls, but these changes were not observed in the hypothalamus. In another study, 12- and 26-month-old mice were administered either an ethanol (8 g/kg in two doses daily) or a control diet by gavage for 3 weeks. The 12-month-old group given the ethanol diet showed an increase in labeled poly-PI which was found largely in the synaptosomal fraction. Surprisingly, the 26-month-old mice given the same ethanol paradigm showed a decrease in labeled poly-PI. Consistent with our previous observations, the 26-month-old mice showed a higher proportion of labeled poly-PI in the synaptosomal fraction as compared to the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biochemistry, University of Missouri, School of Medicine, Columbia 65212.
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002499:Centrifugation, Density Gradient; D002540:Cerebral Cortex / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D008563:Membrane Lipids; D010710:Phosphates; D010713:Phosphatidylcholines; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D000431:Ethanol; D000255:Adenosine Triphosphate