| Abstract | 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. |
| Authors | Martina Velders, Kirsten Legerlotz, Shelley J Falconer, N Susan Stott, Christopher D McMahon, Heather K Smith
(Affiliation: Department of Sport and Exercise Science, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand.)
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| Journal | Experimental physiology
(Exp Physiol)
Vol. 93
Issue 12
Pg. 1273-83
(Dec 2008)
ISSN: 0958-0670 England |
| PMID | 18603602
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Botulinum Toxin Type A
- Muscle Proteins
- RNA, Messenger
|
| Topics |
- Adaptation, Physiological
- Animals
- Body Weight
- Botulinum Toxin Type A
(administration & dosage)
- Disease Models, Animal
- Gene Expression Regulation
- Injections, Intramuscular
- Male
- Mechanotransduction, Cellular
(genetics)
- Muscle Proteins
(genetics, metabolism)
- Muscle, Skeletal
(metabolism, pathology, physiopathology)
- Organ Size
- Paralysis
(chemically induced, genetics, metabolism, physiopathology)
- Physical Exertion
- RNA, Messenger
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reverse Transcriptase Polymerase Chain Reaction
- Sarcomeres
(metabolism)
- Time Factors
|
