Treatment with lithium carbonate does not improve disease progression in two different strains of SOD1 mutant mice.
It has been shown that chronic treatment with lithium carbonate (Li(2)CO(3)) in presymptomatic SOD1G93A transgenic male mice, a model of ALS, was able to remarkably increase their lifespan through the activation of autophagy and the promotion of mitochondriogenesis and neurogenesis. This prompted us to test the lithium effect also in female SOD1G93A mice with two phenotypes of different disease severity. Female SOD1G93A mice of C57BL/6J or 129S2/Sv genetic background were treated daily with Li(2)CO(3) 37 mg/kg (1 mEq/kg) i.p. starting from age 75 days until death. Grip strength, latency to fall on rotarod and body weight were monitored twice weekly. At the time of death the spinal cord was removed to assess the number of motor neurons and to measure the expression of a marker of autophagy (LCII) and the activity of mitochondrial complex IV. We observed a significant anticipation of the onset and reduced survival in 129Sv/G93A and no effect in C57/G93A mice treated with lithium compared to vehicle treated mice. Moreover, lithium neither exerted neuroprotective effects nor increased the expression of LCII and the activity of mitochondrial complex IV in the spinal cord. The present study does not identify any therapeutic or neuroprotective effect of lithium in SOD1G93A female mice.
Pizzasegola
Chiara
C
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Caron
Ilaria
I
Daleno
Cristina
C
Ronchi
Anna
A
Minoia
Claudio
C
Carrì
Maria Teresa
MT
Bendotti
Caterina
C
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015996:Survival Rate
D018692:Antimanic Agents; D015415:Biomarkers; C000606290:SOD1 protein, human; D016651:Lithium Carbonate; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1