Partial lithium-associated protection against apoptosis induced by C2-ceramide in cerebellar granule neurons

PRIMARY cultures of cerebellar granule neurons, maintained in a serum-containing medium, underwent apoptosis when exposed to C-2-ceramide, as assessed by mitochondrial reduction of MTT and intranucleosomal DNA fragmentation. After an 18 h exposure to 50 mu M C-2-ceramide, cell viability decreased by 25-40%. Addition of lithium together with C-2-ceramide resulted in a partial protection of apoptosis, which was maximal at 5 mM lithium (37% protection). When lithium was added 5 h before the apoptotic stimulus the neuroprotective effect of the ion was clearly increased (66% protection). This effect was not due to intracellular inositol depletion or inhibition of NMDA receptors. Our data broaden the nature of apoptotic insults being reversed by lithium, stressing the neuroprotective effects of the ion. (C) 1998 Lippincott Williams & Wilkins.