Associations between central and peripheral measures of phospholipid breakdown revealed by cerebral 31-phosphorus magnetic resonance spectroscopy and fatty acid composition of erythrocyte membranes

Abstract:

ABSTRACT: Abnormal neuronal membrane phospholipid metabolism is increasingly recognized as being of central importance to a number of neuropsychiatric disorders. Currently, two important indices of membrane phospholipid metabolism tend to be measured: the ratio of the areas of the phosphomonoester (PME) and phosphodiester (PDE) peaks from in vivo cerebral phosphorus magnetic resonance spectroscopy (31P MRS) studies; and erythrocyte membrane fatty acid concentrations. Thus far, there have been no studies comparing these two indices to ascertain the extent to which they agree. The authors measured these indices in nine normal adults. Spectral localization was achieved using four- dimensional chemical shift imaging methods and erythrocyte membrane fatty acid concentrations (from blood samples taken at the time of scanning) were measured using gas liquid chromatography. Levels of PDE (an index of phospholipid catabolism), measured using cerebral 31P MRS, were significantly correlated with reduced concentrations of the highly unsaturated fatty acids docosahexaenoic acid (DHA) (r = -0.68, p < 0.05) and eicosapentaenoic acid (EPA) (r -0.78, p < 0.02). No significant correlations were found between peripheral concentrations of any highly unsaturated fatty acids and PME levels, nor between their essential fatty acid precursors and either PDE or PME levels. Other 31- phosphorus metabolites also showed no significant correlations with the blood fatty acid measures. The correlations between central measures of PDE and peripheral measures of DHA and EPA provide validation of cerebral 31P MRS as a non-invasive technique for the study of membrane phospholipid metabolism in vivo.

NON-TECHNICAL SUMMARY

Increasing evidence suggests that membrane phospholipids - which are found in both the brain and the body - are of vital importance to a number of conditions thought to involve disturbances of brain chemistry and thus classified as 'psychiatric' or 'psychological'. Phospholipids are the main component of cell membranes in the both the body and the brain, and their properties are influenced by the fatty acids they contain. For proper functioning, they must contain certain complex omega-3 and omega-6 fats that can only be derived from the diet. These fats are particularly important in the brain.

Direct assessment of membrane phospholipids and fatty acids in the living body and brain is obviously difficult. Measures most often used in research include (1) concentrations in red blood cell membranes (RBC) of different fatty acids, and (2) a special form of brain imaging called 31-Phosphorus Magnetic Resonance Spectroscopy (31-P MRS). Until now, there have been no studies comparing these two indicators to determine the extent to which they agree, so this was our aim.

Both blood fatty acid analysis and 31-P MRS were carried out on 9 healthy adults, and the results compared. Low blood concentrations of the main omega-3 highly unsaturated fatty acids, EPA and DHA, were associated with higher concentrations from the brain imaging measures of phosphodiesters (PDE), an index of membrane phospholipid breakdown. (Both would be consistent with high levels of 'oxidative stress', whereby the fatty acids in membranes are damaged by free radicals.) Correspondence was therefore found between these two methods of assessing some aspects of fatty acid biochemistry, one involving the analysis of peripheral blood samples and the other, the chemical composition of brain tissue using a non-invasive brain imaging technique.