Increased, And Decreased Activity Differentially Alter Neuromuscular Junction Morphology

Abstract

PURPOSE The objective of this study was to directly compare the effects of increased or decreased activity on neuromuscular junction (NMJ) morphology. METHODS Twenty-four young (7 wks old) male Sprague-Dawley rats were randomly assigned to one of three treatment groups (N=8/group). Rats assigned to the increased activity group performed treadmill running 5 d/wk for 10 wks. Animals assigned to the decreased activity group were subjected to muscle unloading for 10 wks. Control rats lived freely in their cages for the same 10 wk period. At the end of the 10 wk intervention, all animals were euthanized before soleus muscles were dissected out, cleared of fat and connective tissue and quickly frozen at resting length. To visualize NMJs, 50 μm thick longitudinal muscle sections were obtained on a cryostat, and stained with rhodamine conjugated bungarotoxin, along with fluorescein labeled RT97 antibody. Bungarotoxin binds specifically to post-synaptic acetylcholine receptors, and RT97 recognizes pre-synaptic nerve terminals. Images of NMJs were collected and analyzed with a confocal microscope. One way ANOVA was used to compare data from the three treatment groups. RESULTS The data showed that in both fast- and slow-twitch myoflbers, exercise training significantly (P < 0.05) amplified pre-synaptic nerve terminal branching without altering post-synaptic structure of the NMJ. In contrast, muscle unloading resulted in diminished (P < 0.05) post-synaptic endplate dimensions without affecting nerve terminal characteristics. CONCLUSIONS These data suggest that although both increased, and decreased activity elicit significant synaptic remodeling, the mechanisms involved appear to be activity specific, as is the nature of the structural adaptations.