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Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice
Published on: October 3, 2011
Atorvastatin treatment attenuates motor neuron degeneration in wobbler mice
Konosuke Iwamoto1, Yasuhiro Yoshii, Ken Ikeda
1Department of Neurology, Toho University Omori Medical Center, 6-11-1 Omorinishi, Otaku, Tokyo, Japan.
Abstract:
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.
Insights
Atorvastatin treatment significantly slowed motor neuron degeneration in wobbler mice, delaying motor deficits by over four weeks. This cholesterol drug demonstrated neuroprotective effects, preserving muscle function and reducing motor neuron loss.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Wobbler mice serve as a model for motor neuron diseases.
- Motor neuron degeneration leads to progressive muscle weakness and atrophy.
- Identifying therapeutic agents to slow neurodegeneration is crucial.
Purpose of the Study:
- To investigate the neuroprotective potential of atorvastatin in wobbler mice.
- To assess the impact of atorvastatin on motor function and neuropathology.
Main Methods:
- Wobbler mice and littermates received atorvastatin or vehicle for 4-8 weeks.
- Motor function was assessed via pull-strength and forelimb deformity.
- Neuropathological and biochemical analyses of muscle and spinal cord were performed.
Main Results:
- Atorvastatin delayed motor deficit progression by over four weeks.
- It suppressed denervation atrophy by 30% and maintained muscle choline acetyltransferase activity.
- Approximately 30% of motor neuron loss was attenuated in atorvastatin-treated mice.
Conclusions:
- Atorvastatin exhibits significant neuroprotective effects in the wobbler mouse model.
- The drug mitigates motor neuron degeneration and associated muscle atrophy.
- Atorvastatin holds promise as a therapeutic intervention for motor neuron diseases.
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