Lithium induces apoptosis in immature cerebellar granule cells but promotes survival of mature neurons.
Lithium (Li+) has been used in the treatment of manic-depressive disorders for several decades. More recently, Li+ has been shown to affect the signaling pathway of various neurotransmitters and growth/neurotrophic factors. We examined the effect of Li+ on the survival of cerebellar granule neurons in culture. Treatment of immature granule cells with Li+ resulted in programmed cell death (apoptosis). The death process is accompanied by DNA fragmentation, a hallmark of apoptosis. Following maturation in vitro, granule neurons are dependent on elevated concentrations of extracellular potassium ([K+]o) for survival. Lowering of [K+]o to physiological levels induces apoptosis. Surprisingly, Li+ prevents death of mature neurons caused by low [K+]o. Moreover, the concentration range at which Li+ exerts its protective effect is the same as that at which it induces apoptosis in immature neurons. Thus, a single agent under similar extracellular conditions has opposing effects on survival, depending on the developmental status of the neuron.
D'Mello
S R
SR
Institute of Neurobiology, CNR, Rome Italy.
Anelli
R
R
Calissano
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects*; D007294:Inositol / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D007294:Inositol; D008094:Lithium; D011188:Potassium