Age-related changes in central nervous system phosphatidylserine decarboxylase activity

Abstract

A significant portion of brain phosphatidylethanolamine (PE) is synthesized by a pathway involving the mitochondrial enzyme phosphatidylserine decarboxylase (PSDC), in a process by which phosphatidylserine (PS) is transferred from the endoplasmic reticulum to mitochondria. Aging changes the fatty acid composition of brain phospholipids, PS and PE being the most affected. The present study was carried out to determine PSDC activity in cerebral cortex (CC) and cerebellum (CRBL) mitochondrial fraction from adult (4-month-old) and aged (30-month-old) rats and to compare these activities with that found in liver. To study the effect of 22:6n-3 content on the PSDC activity, PSs from different sources were prepared: rPS (from bovine retina, containing 36 mol % of 22:6n-3); adPS (from adult rat CC microsomal membranes, with 25 mole % 22:6n-3 content) and agPS (from aged rat CC microsomal membranes, with 21 mole % 22:6n-3 content). For aged CC PSDC, the preferred substrate was agPS (the physiological substrate for aged animals), whereas in adult CC PSDC the substrate preference was inverse (rPS > adPS > agPS). Furthermore, CRBL PSDC does not show any substrate preference based on 22:6n-3 content. CRBL PSDC activity in aged membranes using agPS as substrate is lower than PSDC activity in adult membranes in the presence of adPS. These results indicate that under physiological conditions, cerebellar PSDC is inhibited during aging. Liver PSDC activity showed the same substrate preference in adult and aged rats as adult CC PSDC. These findings lead us to conclude that PSDC activity has a differential tissue-dependent substrate preference characteristic of the aging process.