Abstract
Methylxanthines, such as theophylline, aminophylline and caffeine, are used extensively in the treatment of apnea in the neonatal period, a time of active membrane proliferation and myelination in the human brain. C-6 glial cells in culture are good models of the glia found in human brain during this developmental phase. Because cholesterol is a critical constituent of neural membranes, including myelin, we studied the effect of methylxanthines on biosynthesis of this lipid in cultured C-6 glial cells. Exposure of the cells to theophylline, aminophylline, and caffeine for just 24 hours in a concentration of 1×10-3 M resulted in marked reductions of cholesterol synthesis (from [14C] acetate), i.e. 29, 8 and 37% respectively of control values. Cell growth was not significantly affected by the drugs. Lower concentrations produced inhibitory effects after longer exposure times, e.g. theophylline, 5×10-4 M, caused a 50% reduction in cholesterol synthesis after 72 hours. To determine whether the methylxanthines cause an alteration in the critical rate-limiting enzyme, HMG-CoA reductase, we assayed this enzyme in treated and untreated C-6 glial cells. A marked decrease in reductase activity accompanied the decrease in cholesterol synthesis. The mechanism of this effect is currently under investigation. These data raise the possibility that methylxanthines have a deleterious effect on the development of the human brain.
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Allan, W., Volpe, J. 226 METHYLXANTHINES CAUSE A MARKED REDUCTION IN CHOLESTEROL SYNTHESIS IN CULTURED GLIAL CELLS. Pediatr Res 12 (Suppl 4), 401 (1978). https://doi.org/10.1203/00006450-197804001-00231
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DOI: https://doi.org/10.1203/00006450-197804001-00231