The long range objective of this project is an understanding of the factors wich contribute to the normal development and maintenance of CNS myelin. we propose to study the role of carbonic anhydrase in the physiological processes which give rise to normal adult compact myelin. Procedures have been developed for the solubilization and purification of myelin carbonic anhydrase and for measuring both the activity and the levels of myelin carbonic anhydrase. These procedures will be applied to the study of the rates of synthesis in adult and developing rat brain, in myelin deficient genetic strains of mice and in adrenalectomized rats. An in-depth study of the effects of adrenal steroids on cabonic anhydrase will be carried out to provide information on the physiological mechanisms controlling the low water content of myelin. Information on the possible induction of carbonic anhydrase, and other myelin proteins, by corticosteroids will be provided by a double isotope technique. Spironolactone, an inhibitor of aldosterone, will be used as a probe for mineralocorticoid effects on myelination; metazolamide will be used to study effects of carbonic anhydrase inhibition on the maturation and compositon of developing myelin. These sutides are pertinent to understanding the normal maturation of myelin and thepathophysiology of various forms of hydrocephalus and of a wide variety of demyelinating diseases including multiple sclerosis. Sapirstein, V., Trachtenberg, M., Lees, M.B. and Koul, O.: Regional Development and Fractional Studies on Myelin and other carbonic anhydrases in rat CNS in Myelination and demyelination: Recent Chemical advances. Palo, J. and Riekennen, P., (Eds.), 55-69, 1978. Sapirstein, V.S. and Lees, M.B.: Alteration in carbonic anhydrase and adenylate cyclase in quaking mice. Trans. Amer. Soc. Neurochm. 10: 217, 1979.