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Published on: July 12, 2013
Altered composition of polyunsaturated fatty acyl groups in phosphoglycerides of Down's syndrome fetal brain
Insights
Prenatal brain development in Down syndrome shows altered polyunsaturated fatty acids (PUFA) composition in phospholipids. Specifically, the ratio of (n-3) to (n-6) PUFA is elevated, with increased docosahexaenoic acid and decreased arachidonic acid.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- Down syndrome is associated with altered brain development.
- Lipid peroxidation is enhanced in prenatal Down syndrome brain homogenates.
- Polyunsaturated fatty acids (PUFA) are crucial components of brain phospholipids.
Purpose of the Study:
- To investigate the composition of PUFA in ethanolamine phosphoglycerides (EPG) and serine phosphoglycerides (SPG) in the cerebral cortex of prenatal Down syndrome fetuses.
- To compare PUFA profiles with age-matched controls to identify developmental alterations.
Main Methods:
- Analysis of polyunsaturated acyl groups (PUFA) in ethanolamine and serine phosphoglycerides (EPG and SPG) from cerebral cortex specimens.
- Comparison of PUFA ratios, particularly (n-3) to (n-6) series, between Down syndrome and control fetuses.
- Quantification of specific fatty acids like docosahexaenoic acid (22:6(n-3)) and arachidonic acid (20:4(n-6)).
Main Results:
- Total PUFA percentages in EPG and SPG were not significantly different between Down syndrome and control groups.
- The ratio of (n-3) to (n-6) PUFA was significantly elevated in Down syndrome (0.55 in EPG, 0.97 in SPG) compared to controls (0.32 in EPG, 0.60 in SPG).
- Docosahexaenoic acid (22:6(n-3)) was increased by 54% in EPG and 33% in SPG, while arachidonic acid (20:4(n-6)) was decreased by 16% in EPG and 30% in SPG in Down syndrome fetuses.
Conclusions:
- Prenatal Down syndrome brain exhibits a distorted essential fatty acid metabolism and incorporation into phosphoglycerides.
- The altered balance of docosahexaenoic acid and arachidonic acid in membrane phospholipids may disrupt membrane enzyme function and transport processes.
- These findings suggest a potential biochemical basis for neurodevelopmental differences in Down syndrome.
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.
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