Effect of botulinum toxin A-induced paralysis and exercise training on mechanosensing and signalling gene expression in juvenile rat gastrocnemius muscle.
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 (> or = 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.
Velders
Martina
M
Department of Sport and Exercise Science, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.
Legerlotz
Kirsten
K
Falconer
Shelley J
SJ
Stott
N Susan
NS
McMahon
Christopher D
CD
Smith
Heather K
HK
D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007273:Injections, Intramuscular; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D010243:Paralysis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005082:Physical Exertion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012518:Sarcomeres / Q000378:metabolism; D013997:Time Factors
D009124:Muscle Proteins; D012333:RNA, Messenger; D019274:Botulinum Toxins, Type A