Search

Publisher Summary The potential of the adult brain for lipid metabolism has always been regarded as limited. Recently, the admission of newer evidence has challenged this static concept for neural metabolism. Studies with radioactive nutrients on the intact animal are difficult to interpret because of the protective mechanisms (blood-brain barrier) of the brain, which controls the movement of substances into and out of the neural tissue. Thus the unavailability of injected precursors to become incorporated into compounds of the central nervous system has been interpreted by early investigators as indicative of a limited metabolic potentiality. Through special techniques and experimental designs, recent studies have mitigated against this static metabolic picture for neural tissue, which now indicates extensive metabolic potentials. Pursuing the problems of cholesterol biosynthesis in various tissues by simultaneous use of selected 14 C- and 3 H-precursors, it has been previously reported that acetate was a poor choice for the study of the brain cholesterol formation. In this and similar studies, glucose is shown to be a better carbon source for brain cholesterol than acetate. It is of interest, therefore, to examine the contribution of a non-carbohydrate labeled substance and glucose as both became incorporated into the sterol of the developing mouse brain. Mice representing three age groups are simultaneously injected with acetate-2- 3 H and glucose-U- 14 C and the incorporation of these labeled nutrients into brain cholesterol was measured in this chapter.

Publisher Summary This chapter discusses the effect of chemical and physical agents on brain cholesterol. The brain represents the largest repository of body cholesterol however relatively little is known about its metabolism and even less about its function and role within the central nervous system. It has been suggested that cholesterol turnover may be more rapid in some areas than in others. In view of new evidence that indicates both biosynthetic capacity and turnover ability of cholesterol in adult brain, studies dealing with the effect of chemical and physical agents on the constituent have become more rational. That the stability of brain cholesterol was so readily accepted in view of early experiments showing drug effect is difficult to comprehend. Drug stimulants and drug depressants may have their mechanism of action directly or indirectly on brain cholesterol. It is clear from the diversity of chemical structures which affect cholesterol metabolism in general and brain cholesterol in particular that further work will be necessary to relate the mechanisms of drug action on brain cholesterol and brain function.

Publisher Summary This chapter presents a critical review of brain cholesterol metabolism. Modern aspects of brain sterol metabolism are reviewed by Davison and Kabara. Consequently, for this review, the chapter emphasizes only the more recent concepts of brain cholesterol metabolism. To form a backdrop for the discussion of brain cholesterol metabolism, the anatomical and chemical changes taking place in the central nervous system (CNS) during growth and development are outlined in the chapter. Because sex, nutrition, precursor used, diurnal variation, etc., influence biosynthetic rates as measured, their influence should be considered in any developmental analysis of metabolic capacity within the CNS. Whole brain values obtained in the past from animals injected with a radioactive precursor did not reflect metabolism or changes in metabolism of anatomical areas, individual cells or organelles. Although accurate information is not available, conclusions based on such comparisons lead to statements in the literature which are very difficult to change, even in the face of new and more conclusive data.