Partial lithium-associated protection against apoptosis induced by C-2-ceramide in cerebellar granule neurons

PRIMARY cultures of cerebellar granule neurons, maintained in a serum-conta ining 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 parti al protection of apoptosis, which was maximal at 5 mM lithium (37% protecti on). When lithium was added 5 h before the apoptotic stimulus the neuroprot ective effect of the ion was clearly increased (66% protection). This effec t was not due to intracellular inositol depletion or inhibition of NMDA rec eptors. Our data broaden the nature of apoptotic insults being reversed by lithium, stressing the neuroprotective effects of the ion. (C) 1998 Lippinc ott Williams & Wilkins.