OBJECTIVETo study the effects of valproate acid (VPA) on serum lipid and leptin levels and cerebral cortex in juvenile and adult rats.

METHODSTwenty healthy juvenile female Sprague-Dawley (SD) rats (21-day-old) and twenty healthy adult female SD rats (2-month-old) were randomly divided into four groups (n=10 each): juvenile control, juvenile VPA, adult control and adult VPA. Juvenile and adult VPA groups were fed with VPA 200 mg/kg daily, while the two control groups were fed with normal saline. The body weights were recorded weekly. Six weeks after feeding, serum and brain samples were obtained. Serum lipid levels including total cholesterol (TC), triglycerides (TG) and lower density lipoprotein cholesterol (LDL-C) were determined. Serum leptin (LEP) levels were measured by radioimmunoassay (RIA). Myelin staining and Nissl staining were used to evaluate the changes of brain tissues.

RESULTSThe weight and serum LEP and lipid levels in both juvenile and adult VPA groups increased significantly compared with those in the control groups (P<0.05). The juvenile VPA group had more increased serum LEP and lipid levels than the adult VPA group (P<0.05). The Myelin staining showed that the average fiber density in the VPA groups was significantly lower than that in the control groups (P<0.05). The Nissl staining showed that the number of toluidine blue staining neurons in the VPA groups was not statistically different from the control groups.

CONCLUSIONSVPA may increase serum LEP and lipid levels in both juvenile and adult rats, and more increased levels may be found in juvenile rats. Long-term VPA treatment may have an adverse effect on brain myelination, but no effect on neurons.