Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons

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

Abstract

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.

Más información

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

10.1046/j.1399-5618.2003.00090.x

Notas: ISI