Chronic denervation syndromes such as the post-polio syndrome are associated with progressive muscle weakness and fatigue after motoneuron death. Neither the etiology nor the management of these syndromes is clear. To address this issue, we partially denervated rat hindlimb muscles for 1 or 12 months and examined whether chronically enlarged motor units (MUs) become destabilized with time and further destabilized by daily running on exercise wheels. MU enlargement, measured electrophysiologically and morphologically was significantly reduced at 12 months in extensively denervated muscles, and to a lesser extent in moderately denervated muscles, as compared to the findings at 1 month. A 1-month period of running exercise further reduced the size of the chronically enlarged MUs in the extensively denervated muscles. We have therefore (1) successfully established a rat model of time-related MU size reduction, in which destabilization of chronically enlarged MUs results in loss of axonal terminals, and (2) demonstrated that nonphysiological activity has small but significant effects of further destabilizing the chronically enlarged MUs.
Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000--000, 2002 DOI 10.1002/mus.10057