Effects of hindlimb unloading on neuromuscular development of neonatal rats

We hypothesized that hindlimb suspension unloading of g-day-old neonatal ra ts would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not exte nsor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and ret urned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control f or isolation from the dam, the remaining five littermates were removed on t he same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar A TPase histochemistry and immunostaining for embryonic, slow, fast IIA and f ast IIB isomyosins. The percentage of multiple innervation and the complexi ty of singly-innervated motor terminal endings were assessed in silver/chol inesterase stained sections. Unique to the soleus, unloading accelerated pr oduction of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple i nnervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation thro ugh nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexp ectedly, in the EDL of unloaded rats, transition from embryonic to fast myo sin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. T hese results demonstrate that neuromuscular development of both weightbeari ng and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading. (C) 2000 Elsevier Science B.V. All rights reserved.