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Intramuscular injections of the paralytic botulinum neurotoxin A (Btx) and physical exercise are used in the treatment of chronic spasticity in children with cerebral palsy. We tested whether Btx-induced paralysis and/or exercise training would have differential effects on the expression of mechanosensing and signalling genes implicated in the adaptive remodelling of skeletal muscle. Juvenile (29-day-old) male rats were injected with Btx or saline (NoBtx) into the right gastrocnemius and housed in standard cages (NoEx) or with running wheels (Ex), for 3 weeks ( n= 6 per group). The mRNA expression of nine sarcomere-associated genes in the medial gastrocnemius was then determined by quantitative reverse transcriptase-polymerase chain reaction. The Btx-injected muscles weighed 50% less than NoBtx muscles, but Ex had no effect on the wet mass of Btx or NoBtx muscles. Atrogenic MuRF1, sarcomeric Titin and myogenic MyoD were upregulated (2-fold) with the elimination of contractile activity in Btx muscle. Expression of CARP, Ankrd2 and MLP was increased with mechanical stimuli associated with Btx (5- to 10-fold) or Ex (2- to 4-fold). Expression of CARP and Ankrd2 increased synergistically in Btx–Ex muscle (≥20-fold), indicating that these genes may be sensitive to passive stretch of the sarcomeric I-band region of titin to which their proteins bind. Tcap, Myopalladin and Atrogin1 were not, or were no longer responsive to the altered mechanical stimuli after 3 weeks of Btx or Ex. The expression of Ankrd2, CARP and MLP may thus be enhanced by passive stretch within the Btx-paralysed and/or exercising gastrocnemius and contribute to adaptations, other than muscle mass, in juvenile rats. [ABSTRACT FROM AUTHOR]

The aims of this study were to characterize the pattern of voluntary activity of young rats in response to resistance loading on running wheels and to determine the effects of the activity on the growth of six limb skeletal muscles. Male Sprague–Dawley rats (4 weeks old) were housed individually with a resistance running wheel (R-RUN, n= 7) or a conventional free-spinning running wheel (F-RUN, n= 6) or without a wheel, as non-running control animals (CON, n= 6). The torque required to move the wheel in the R-RUN group was progressively increased, and the activity (velocity, distance and duration of each bout) of the two running wheel groups was recorded continuously for 45 days. The R-RUN group performed many more, shorter and faster bouts of running than the F-RUN group, yet the mean daily distance was not different between the F-RUN (1.3 ± 0.2 km) and R-RUN group (1.4 ± 0.6 km). Only the R-RUN resulted in a significantly ( P < 0.05) enhanced muscle wet mass, relative to the increase in body mass, of the plantaris (23%) and vastus lateralis muscle (17%), and the plantaris muscle fibre cross-sectional area, compared with CON. Both F-RUN and R-RUN led to a significantly greater wet mass relative to increase in body mass and muscle fibre cross-sectional area in the soleus muscle compared with CON. We conclude that the pattern of voluntary activity on a resistance running wheel differs from that on a free-spinning running wheel and provides a suitable model to induce physiological muscle hypertrophy in rats. [ABSTRACT FROM AUTHOR]