Effect of hypoxic-ischemic injury on serine palmitoyltransferase activity in the developing rat brain.

BACKGROUND Sphingolipid metabolism is strongly associated with central nervous system myelination. Ceramide is the most active of the sphingolipid metabolites. On the basis of ceramide biosynthesis indicated by serine palmitoyltransferase activity and cerebroside generated by ceramide, the evaluation of serine palmitoyltransferase activity in developing brains or hypoxic-ischemic damaged brains is worthwhile. METHODS Using a scintillation counter, we assessed serine palmitoyltransferase activity, a rate-limiting enzyme of sphingolipid metabolism, in the brains of developing rats and compared the activity with hypoxic-ischemic brains, using the method of Rice on postnatal day 7 (P7). RESULTS In the control groups, serine palmitoyltransferase activity was detected in the microsomal fraction of whole brain homogenates from P4, which was earlier than the initial expression of myelin-specific proteins such as myelin basic protein and proteolipid protein on immunochemistry. Serine palmitoyltransferase activity increased along with development on P8, P10, P14 and P21. However, hypoxic-ischemic brains showed lower serine palmitoyltransferase activity than control brains on P8, P10, P14 and P21. CONCLUSIONS These results suggest that increase in serine palmitoyltransferase activity before myelin-specific protein expression may be an initial step in myelinogenesis and a decline in serine palmitoyltransferase activity in hypoxic-ischemic brains may be one of the major causes of delayed myelination.