MORPHOLOGICAL EFFECTS OF CILIARY NEUROTROPHIC FACTOR TREATMENT DURINGNEUROMUSCULAR SYNAPSE ELIMINATION

In adult skeletal muscles, exogenous ciliary neurotrophic factor (CNTF ) induces axons and their nerve terminals to sprout, CNTF also regulat es the amount of multiple innervation in developing skeletal muscles d uring synapse elimination, maintaining multiple innervation of muscle fibers. While CNTF may maintain multiple innervation by regulating dev elopmental synapse elimination, it is also possible that CNTF induces the formation of new multiple innervation through a sprouting response , In this study I examined morphologically the effects of CNTF during synapse elimination in the extensor digitorum longus (EDL) muscle, Rat pups received injections of CNTF in one leg and vehicle in the other either early [postnatal day 7 (P7)-P13] or late (P14-P20) in developme nt, The early treatment period corresponds to that time when the patte rn of innervation in the EDL is converted from predominantly multiple to single innervation. The late treatment period is at the end of syna pse elimination for the EDL but corresponds to the major period of syn apse elimination in the levator ani (LA), allowing a comparison of eff ects on these two muscles from the same animals. On the day after the final injection, EDL muscles were dissected and stained with tetranitr oblue tetrazolium and the resulting pattern of innervation was assesse d. The present findings indicate that only the early CNTF treatment re gulates the level of multiple innervation in the EDL, Moreover, the ef fect of early CNTF treatment was local, affecting multiple innervation only in the EDL from the CNTF-treated leg, CNTF injected during the l ate treatment period had no apparent effects on the EDL but had a pote nt effect on the pattern of innervation in the LA, significantly incre asing the level of multiple innervation in this muscle. Thus, CNTF aff ected multiple innervation in these two muscles only if provided durin g the period when single innervation normally develops, There was no e vidence to indicate that CNTF induced axons or their terminals to spro ut during either treatment period, In conclusion, CNTF increases the l evel of multiple innervation, probably by regulating synapse eliminati on, and skeletal muscles themselves may be an important target site fo r CNTF action, Presumably, the sprouting response to CNTF found in adu lt muscle develops sometime after P21. (C) 1996 John Wiley & Sons, Inc .