Effect of valproate on lipogenesis in neonatal rat brain

The effect of valproate on lipogenesis in brain slices from early neonatal rats was studied. The rate of lipid synthesis from lactate and 3-hydroxybutyrate, but not from glucose, was decreased significantly by 1 mM valproate. Separation by high performance liquid chromatography of brain lipids showed that valproate inhibited the synthesis of major phospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine) from lactate and major sterols (desmosterol, cholesterol and lanosterol) from lactate and 3-hydroxybutyrate. Valproate did not affect sterol synthesis but slightly enhanced phospholipid synthesis from glucose. However, the ratio of phosphatidylserine/phosphatidylethanolamine synthesis was decreased from lactate, glucose and 3-hydroxybutyrate, suggesting that valproate changes phospholipid composition of brain structures. These changes may contribute to the pharmacological action of the drug.