The biochemical and morphological response of hydrolytic enzymes in the developing brain to hypocholesterolemic agents.

Administration of hypocholesterolemic agents to developing rats has been found to selectively induce brain hydrolases. Certain regimes also caused an appreciable increase in total brain protein content. The hypocholesterolemic agents AY-9944 and zuclomiphene were tested individually and in combination. A fourth type of treatment utilized the above drugs in combination with Triparanol. Whenever AY-9944 was used, singly or in combination with other compounds, the beta-glucuronidase activity of developing brain was increased. Acid phosphatase and total brain protein were increased in animals treated with AY-9944 plus zuclomiphene or AY-9944 plus zuclomiphene and Triparanol. Neither AY-9944 nor zuclomiphene alone significantly affected brain total protein or acid phosphatase. Electron microscopic examination of tissue specifically reacted for acid phsophatase demonstrated that the increased enzyme activity was localized in cells in the perivascular spaces. Alkaline phosphatase and N-acetyl-beta-glucosaminidase, two other hydrolytic enzymes assayed, seemed to be much less influenced by the drug treatments.