Lack of Catabolism of Brain Cholesterol

Since direct intracranial injections of precursors indicate that cholesterol is synthesized in the brain at all ages, there must be a mode of disposal also. The sterol nucleus itself is not degraded by mammalian systems but the side chain can be metabolized. [26-14C] cholesterol was therefore injected directly into the brain of 8- to 19-day-old rats which were sacrificed at the end of 24 hr, 1 week and 2 weeks after injection. The results indicate that, irrespective of the interval between injection and sacrifice, all of the radioactivity was found in the free cholesterol or the cholesterol component of the sterol esters. No radioactivity was found in the fatty acids of the phospholipids. We therefore conclude that the side chain of the cholesterol does not get metabolized to propionyl CoA, which in turn, could lead to fatty acid synthesis. Radioactivity in the serum, even after 2 weeks, indicates that there must be a slow but steady exchange between the brain and the blood that would explain the route of exit for brain cholesterol.