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Low Copper Status of Rats Affects Polyunsaturated Fatty Acid Composition of Brain Phospholipids, Unrelated to Neuropathology^1,2,

Department of Biochemistry, University of Missouri, Columbia, MO 65211

To determine the molecular basis of the neuropathology of copper deficiency, brain lipid composition was determined in second-generation copper-deficient rats. Non-parous female rats were fed a low copper diet (0.5 mg Cu/kg) or a control diet (10 mg Cu/kg) during gestation and lactation, and the offspring were continued on the respective diets to 8 wk of age. In one experiment the source of carbohydrate was 15% starch and 52.6% sucrose, and in another experiment sucrose and glucose were compared in a factorial design. The source of carbohydrate had no effect on copper status. Myelin concentration was estimated by isolation, by 2',3'-cyclic nucleotide phosphodiesterase activity, and by concentration of 20:1 (n-9). Fatty acid compositions of the phospholipid fractions of brain parts and of myelin were determined. Copper deficiency reduced myelin concentration slightly in the midbrain region and increased the proportion of linoleic acid [18:2(n-6)] in both brain and isolated myelin. In the cerebellum the long-chain polyunsaturated fatty acids, particularly 22:6(n-3), were lower. Approximately one-half of the copper-deficient rats developed Parkinson-like signs and had low striatal dopamine, but neither myelin content nor brain fatty acid composition was associated with the neuropathology.

KEY WORDS: • copper • rats • brain lipids • myelin • neuropathology

¹ Supported in part by National Institutes of Health Grant NS-25395.

² Contribution No. 11403 from the Missouri Agricultural Experiment Station.

³ Part of a Ph.D. dissertation completed while Dr. Sun was on leave from the National Yang-Ming Medical College, Taipei, Taiwan.

⁴ To whom correspondence should be addressed.

Manuscript received 15 April 1991. Revision accepted 8 July 1991.