Clenbuterol retards loss of motor function in motor neuron degeneration mice

Motor neuron degeneration (mnd) mice exhibit lysosomal accumulation of lipofuscin-like material that is associated with progressive loss of motor function and strength. Motor dysfunction scores at 8.5-9 months of age were highly correlated with the occurrence of abnormal spinal motor neurons with eccentric nuclei, although the total numbers of motor neurons were not significantly reduced. Nuclear eccentricity is a characteristic of the axon reaction that results from injury and subsequent compensatory axonal sprouting indicating axonal/synaptic dysfunction in mud motor neurons. Treatment with clenbuterol, a beta(2)-adrenoceptor agonist that can enhance regeneration of motor neuron axons, opposed the development of motor deficits in parallel with a reduced proportion of motor neurons with eccentric nuclei consistent with improved synaptic function. Clenbuterol also opposed decreases in grip strength and muscle mass suggesting beta(2)-agonist treatment as a potential therapeutic modality for lipofuscinoses. (C) 2004 Elsevier Inc. All rights reserved.