Phospholipid molecular species composition of developing fetal guinea pig brain

Adequate accumulation of polyunsaturated essential fatty acids, in particular docosahexaenoic acid (22:6n-3), into membrane phospholipids is critical for optimal fetal brain development. This process is maximal during the period of rapid neurite outgrowth, neuritogenesis, which precedes the major growth phase, myelination. There is no information about differential changes during gestation to individual brain phospholipid molecular species which contain 22:6n-3. Such details of brain development would be concealed by total fatty acid analysis of isolated phospholipid classes. We have detailed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecular species compositions in developing fetal guinea pig brain. Total brain PC concentration increased substantially between 40 and 68 (term) d of gestation, corresponding to myelination, while PE increased in a biphasic manner between 25-35 d, which was coincident with onset of neuritogenesis, and 40-68 d. Fetal brain development was accompanied by complex changes in the concentration of individual phospholipid molecular species. During early gestation (25-40 d) 22:6n-3 was enriched in both PC and PE sn-1 16:0 molecular species. However, between 40 d and term there was no further increase in brain PC 22:6n-3 content, while brain PE was significantly enriched in both PE18:1/22:6 and PE18:0/22:6. We hypothesize that accumulation of 22:6n-3 into sn-1 18:1 and 18:0 species represents establishment of a 22:6n-3-containing membrane PE pool which may be turned over more slowly than sn-1 16:0 species. Identification of specific changes in membrane phospholipids which are associated with defined events in brain development may provide a basis for assigning functional roles to individual molecular species.