Altered composition of polyunsaturated fatty acyl groups in phosphoglycerides of Down's syndrome fetal brain.

Abstract

We have observed recently that in vitro lipoperoxidation is enhanced in Down's syndrome brain homogenates of prenatal age. As this may relate to the composition of polyunsaturated acyl groups (PUFA) in phospholipids, we have examined the PUFA of ethanolamine and serine phosphoglycerides (EPG and SPG), which are particularly rich in PUFA, in the same series of cerebral cortex specimens of Down's syndrome and age-matched control fetuses. Although the total percentages of PUFA in the two phosphoglycerides were not altered, compared with controls the ratio of PUFA of the (n-3) series to those of the (n-6) series was very significantly elevated in Down's syndrome, from 0.32 to 0.55 in EPG and from 0.60 to 0.97 in SPG. In particular, docosahexaenoyl, 22:6(n-3), groups were uniformly increased in Down's syndrome compared with controls by 54% and 33% in EPG and SPG, respectively, while arachidonoyl, 20:4(n-6), groups were decreased by 16% and 30%, respectively. Similar changes occur during normal development, but the (n-3) to (n-6) ratio of PUFA in these phosphoglycerides of Down's syndrome at the fifth month of gestation resembled that of normal human cerebral grey matter at term. However, other developmental indices related to PUFA composition were not significantly affected. It seems therefore that in the developing Down's syndrome brain there may be a distortion of the normal transformations of essential fatty acids and of their incorporation into phosphoglycerides. The disproportion between docosahexaenoyl and arachidonoyl groups in membrane phosphoglycerides during prenatal development in Down's syndrome may also result in disturbances of the proper functioning, and the ontogenetic integration, of membrane enzymes and transport processes.