Effects of trans-clomiphene in combination with AY-9944 on rat CNS morphology and biochemistry

Developing rats were injected intraperitoneally twice weekly with a combination of two hypocholesterolemic agents: trans-clomiphene 50 mg per kg body weight, and AY-9944, 5 mg per kg body weight. Treatment was initiated at 5 days of age. Biochemical and electron microscopic examination was carried out on animals sacrificed at 20 days of age. Only rarely were cytoplasmic inclusion bodies seen in the CNS. Biochemical analysis of the brain and spinal cords of treated animals indicated the abnormal accumulation of three sterols, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). The 7-dehydrosterols constituted from 56--66% of the total CNS sterol component. Zymosterol was a relatively minor (2.4--5.0%) component.