Anti-apoptotic Effect of Acetyl-l-carnitine and l-Carnitine in Primary Cultured Neurons

Abstract

Although exogenously administered acetyl−l−carnitine(ALCAR, (2−acetoxy−3−carboxypropyl)−trimethylammonium)and l−carnitine(LC, (3−carboxy−2−hydroxypropyl)−trimethylammonium)prevent brain damage in several ischemic models, the protective mechanism of these compounds remains unclear.Here, we evaluated the effect of ALCAR and LC in primary cultured neurons from the cerebral cortex, striatum and thalamus of 18−day−old rat embryos.Deprivation of the serum from cultured medium for 3 days reduced the number of viable cells and mitochondrial activity and induced cell death with characteristics of apoptosis such as DNA fragmentation, nuclear condensation and histone−DNA release into the cytoplasm.ALCAR(1−100μM)and LC(1−100μM)promoted neuronal survival and mitochondrial activity in a concentration−dependent manner.Moreover, these compounds attenuated DNA fragmentation and nuclear condensation in cultured neurons and significantly decreased histone−DNA release into the cytoplasm.These results indicate that anti−apoptotic actions of ALCAR and LC contribute to their neuroprotective effect.