The acyl composition of rat brain has been shown to be altered by essential fatty acid (EFA) deficiency. Preliminary results in our laboratory have shown that myelin lipid metabolism is altered during EFA deficiency. The present proposal will examine the the effect of EFA deficiency on the synthesis, incorporation, turnover, and recycling of lipids in synaptic membrane and myelin. Pregnant rats will be placed on an EFA-deficient diet and their progeny maintained on the diet after weaning. A control group will be maintained on the same diet except that corn oil will be added to supply EFA. EFA-deficient and control rats will be injected intracranially with radiolabeled lipid precursors. Brain homogenates, derived from rats at several different ages, will be used to isolate microsomes, synaptic membrane and myelin. The rates of synthesis of several lipid classes as well as their rates of incorporation into microsomes, synaptic membrane, and myelin will be determined. In long-term experimnents, EFA-deficient and control rats will be injected at 18 days of age with radiolabeled lipid precursors. Rats will be sacrificed biweekly over a 6-month period and synaptic membrane and myelin isolated. The turnover and recycling of membrane lipids will be analyzed. Parallel studies on liver and isolated liver plasma membrane will indicate whether the effects of EFA deficiency tested are brain-specific. These studies should reveal the points of biochemical lesions in the metabolism of membrane lipids that result from EFA deficiency, and contribute to the biochemical understanding of how EFA deficiency can result in clinical pathology.
| Miller, S L; Otvos-Papp, E; Prichett, W et al. (1989) Detection and partial biochemical characterization of a novel 57,500 dalton protein in rat brain myelin. J Neurosci Res 22:262-8 |
