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- Title
Motor neurone targeting of IGF-1 prevents specific force decline in ageing mouse muscle.
- Authors
Payne, Anthony M.; Zhenlin Zheng; Messi, María Laura; Milligan, Carol E.; González, Estela; Delbono, Osvaldo
- Abstract
IGF-1 is a potent growth factor for both motor neurones and skeletal muscle. Muscle IGF-1 is known to provide target-derived trophic effects on motor neurones. Therefore, IGF-1 overexpression in muscle is effective in delaying or preventing deleterious effects of ageing in both tissues. Since age-related decline in muscle function stems partly from motor neurone loss, a tetanus toxin fragment-C (TTC) fusion protein was created to target IGF-1 to motor neurones. IGF-1–TTC retains IGF-1 activity as indicated by [3H]thymidine incorporation into L6 myoblasts. Spinal cord motor neurones effectively bound and internalized the IGF-1–TTC in vitro. Similarly, IGF-1–TTC injected into skeletal muscles was taken up and retrogradely transported to the spinal cord in vivo, a process prevented by denervation of injected muscles. Three monthly IGF-1–TTC injections into muscles of ageing mice did not increase muscle weight or muscle fibre size, but significantly increased single fibre specific force over aged controls injected with saline, IGF-1, or TTC. None of the injections changed muscle fibre type composition, but neuromuscular junction post-terminals were larger and more complex in muscle fibres injected with IGF-1–TTC, compared to the other groups, suggesting preservation of muscle fibre innervation. This work demonstrates that induced overexpression of IGF-1 in spinal cord motor neurones of ageing mice prevents muscle fibre specific force decline, a hallmark of ageing skeletal muscle.
- Subjects
MUSCULOSKELETAL system; MUSCLES; BONES; NEURONS; INSULIN-like growth factor-binding proteins
- Publication
Journal of Physiology, 2006, Vol 570, Issue 2, p283
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2005.100032