Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons.
OBJECTIVE
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 microM 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.
Jordà
E G
EG
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Verdaguer
E
E
Morano
A
A
Jiménez
A
A
Canudas
A M
AM
Camins
A
A
Pallàs
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology*; D003078:Colchicine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003124:Colorimetry; D005434:Flow Cytometry; D006074:Gout Suppressants / Q000008:administration & dosage / Q000494:pharmacology*; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006074:Gout Suppressants; D018696:Neuroprotective Agents; D016651:Lithium Carbonate; D003078:Colchicine