Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons

Jorda, EG; Verdaguer, E; Morano, A; Jimenez, A; Canudas, AM; Camins, A; Pallas, M


Objectives: Here we evaluated the neuroprotective effects of two well-known mood stabilizers, lithium and valproic acid (VPA), against colchicine neurotoxicity in cerebellar granule cells (CGNs). Methods: The CGNs were differentiated for 7 days, pretreated with lithium or VPA for 24 h and after colchicine 1 muM was added. Cellular damage was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) method and apoptosis in CGNs was characterized by chromatin condensation and DNA fragmentation. Results: Incubation with lithium (1-5 mM) attenuated this apoptosis markedly, in a dose-dependent way however, the addition of VPA (0.5-2 mM) did not protect CGNs. Colchicine-induced apoptosis is mediated through the activation of caspase-3. An increase in caspase-3 activity was detected within 18 h and was blocked in presence of lithium 5 mM. Conclusions: Our data indicate that lithium treatment is selectively neuroprotective; however, in our experimental conditions VPA did not protect CGNs from apoptosis induced by colchicine. Our results support the hypothesis that distinct pathways mediate the neuroprotective effects of lithium and VPA.

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Título según WOS: ID WOS:000220099300007 Not found in local WOS DB
Título de la Revista: BIPOLAR DISORDERS
Volumen: 6
Número: 2
Editorial: Wiley
Fecha de publicación: 2004
Página de inicio: 144
Página final: 149


Notas: ISI