Time course of biosynthetic cholesterol in the adult rat brain

Abstract

In a first experiment, the time course of biosynthetic cholesterol was studied in the whole brain of adult rats, 1 h to 15 months after an intraventricular injection of 5-[ 14C]mevalonic acid. Radioactivities of nonsaponifiable compounds, sterols and cholesterol purified by gas-liquid chromatography were measured in the brain and those of precursor sterols and squalene fraction were calculated. In the other experiments, only cholesterol radioactivities were measured from 3 days to 1–3 months after injection (1) in the whole brain and in a piece of skull, (2) in the cerebellum and cerebral hemispheres and (3) in a fraction of whole brain homogenate and in cerebral myelin. The most striking results are the following: 1. Brain cholesterol specific radio-activity reaches two maxima, one at 3 days, and the other, slightly lower, at 1 month after injection. 2. After these two peaks, brain cholesterol specific radioactivity decreases as an exponential function of time, with a slope of 0.004 day −1. 3. Cholesterol specific radioactivity of myelin increases up to 40 days after injection whereas that of the other subcellular fractions decreases up to 6 days and increases from 6 to 40 days after injection. Two complementary explanations of these results are discussed. The first involves the existence of two groups of subcellular structures, those of group 1 exchanging their cholesterol with that of plasma, those of group 2 exchanging their cholesterol between themselves and with cholesterol of the first group. The second interpretation involves two chains of biosynthesis for brain cholesterol, working at different rates.