Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis.
Mice bearing the mutated gene for Cu/Zn superoxide dismutase (G93A) are a good model for human amyotrophic lateral sclerosis (ALS). They develop progressive limb paralysis paralleled by loss of motor neurons of the cervical and lumbar spinal cord, which starts at 3-3.5 months of age and ends with death at 4-5 months. Several treatments have been attempted to delay clinical symptoms and to extend lifespan, and some have had modest beneficial effects. One such treatment, based on long-term administration of valproic acid (VPA), resulted in controversial results. We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan. Recently, the hypothesis has been put forward that a deficiency of retinoic acid (RA) and its signaling may have a role in ALS. We report that long-term dietary supplementation with RA has no effect on the decrease of the cholinergic marker in the spinal cord, but it significantly shortens lifespan of G93A mice.
Crochemore
Cristophe
C
Department of Biology, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
Virgili
Marco
M
Bonamassa
Barbara
B
Canistro
Donatella
D
Pena-Altamira
Emiliano
E
Paolini
Moreno
M
Contestabile
Antonio
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D000821:Animal Feed; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018682:GABA Agents / Q000494:pharmacology*; D018628:Gene Dosage; D006801:Humans; D008017:Life Expectancy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000188:drug therapy / Q000401:mortality; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014212:Tretinoin / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018682:GABA Agents; C000606290:SOD1 protein, human; D014212:Tretinoin; D014635:Valproic Acid; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase