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.
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
E G
EG
Jordà
E
E
Verdaguer
A
A
Morano
A
A
Jiménez
A M
AM
Canudas
A
A
Camins
M
M
Pallàs
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