Atorvastatin treatment attenuates motor neuron degeneration in wobbler mice.
We aimed to study whether atorvastatin treatment can retard motor neuron degeneration in wobbler mice. Wobbler mice and their normal littermates were fed 0.01% atorvastatin-mixed food (10 mg/kg/day) or regular food from age 3-4 weeks of disease onset for four weeks (n=10/group) or more than eight weeks (n=10/group). Motor function was evaluated by pull-strength and deformity scale of the forelimbs. For those symptomatic assessment and body weight were measured weekly. Neuropathological and biochemical changes of the biceps muscle and the cervical cord were analyzed at four weeks after treatment. Compared to vehicle, atorvastatin-treated wobbler mice delayed progression of forelimb motor deficits by more than four weeks. Wobbler mice significantly increased body weight from three weeks post-treatment of atorvastatin, compared with vehicle (p<0.05). Atorvastatin administration suppressed denervation atrophy at 30% (p<0.01), maintained choline acetyl transferase activities of the biceps muscle (p<0.05), and attenuated approximately 30% loss of motor neurons in wobbler mice (p<0.01). Atorvastatin fed to normal littermates did not influence body weight gain, neuropathological and biochemical findings. These data suggest that atorvastatin has neuroprotective effects on denervating muscles and degenerating motor neurons in wobbler mice.
Iwamoto
Konosuke
K
Department of Neurology, Toho University Omori Medical Center, 6-11-1 Omorinishi, Otaku, Tokyo, Japan.
Yoshii
Yasuhiro
Y
Ikeda
Ken
K
D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology*; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology; D009468:Neuromuscular Diseases / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin