A single-dose resveratrol treatment in a mouse model of amyotrophic lateral sclerosis.
The underlying causes of denervation of the neuromuscular junction and eventual motor neuron death in amyotrophic lateral sclerosis (ALS) have not been resolved. The superoxide dismutase 1 (SOD1)(G93A) mutant mouse is a frequently used animal model of ALS. We hypothesized that resveratrol (RSV), a polyphenolic molecule that enhances mammalian NAD(+)-dependent SIRT1 deacetylases and may increase life span, would improve motor function and survival in the SOD1 mouse model via modulation of p53 acetylation. Data were collected for mean survival times, neuromuscular performance on the ROTOR-ROD™ (San Diego Instruments, San Diego, CA, USA), body weight, and p53 acetylation. Mean survival times were not statistically different (P=.23) between control and experimental (RSV-fed) groups (mean +/- SD, control [n=11] 138 +/- 6 days vs. experimental [n=10] 135 +/- 8 days). Performance was not significantly different between groups at time points corresponding to 50%, 80%, and 90% mean life span (P=.46), nor did RSV treatment attenuate body weight loss. Thus although manipulation of SIRT1 deacetylase activity has effects at the protein level in healthy aging organisms, we conclude that RSV treatment does not lead to functional improvement or increased longevity in a mouse model of ALS. We speculate that RSV-mediated modulation of p53 acetylation is either incapable of increasing or insufficient to increase motor performance and longevity in this model of ALS.
Markert
Chad D
CD
Department of Neurology, Wake Forest University, Winston-Salem, North Carolina 27157, USA. cmarkert@wfubmc.edu
Kim
Eunkuk
E
Gifondorwa
David J
DJ
Childers
Martin K
MK
Milligan
Carol E
CE
D000107:Acetylation / Q000187:drug effects; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004195:Disease Models, Animal; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011597:Psychomotor Performance / Q000187:drug effects; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D056564:Sirtuin 1; D000077185:Resveratrol