NGF, BDNF, NT-3, and GDNF mRNA Expression in Rat Skeletal Muscle following Denervation and Sensory Protection

Abstract

Poor muscle and nerve functional recovery after nerve damage is a serious clinical problem, particularly if there is prolonged delay before nerve-muscle contact is reestablished. Our previous studies showed that sensory nerve cross-anastomosis (sensory protection) provides support to the denervated muscle. In the present study, we analyzed neurotrophic factor mRNA expression by RT-PCR in denervated rat gastrocnemius muscle receiving sensory protection with the saphenous nerve, compared to normal innervated muscle, to denervated muscle, and to denervated muscle repaired immediately with the peroneal (motor) nerve, after periods of 3 days to 3 months. No significant differences in mRNA levels of beta-actin, nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3 were found between the sensory protection treatment and the denervated or the motor repair groups. However, sensory protection resulted in levels of muscle glial cell line-derived neurotrophic factor mRNA expression that were lower than in denervated muscle and higher than in muscle given immediate motor repair. These results demonstrate that glial cell line-derived neurotrophic factor mRNA is elevated following denervation but is partially down-regulated by sensory protection. Our study suggests that sensory protection provides a modified trophic environment by modulating neurotrophic factor synthesis in muscle.

Fibrin matrices with affinity‐based delivery systems and neurotrophic factors promote functional nerve regeneration

“…This observation further suggests that controlled GDNF release at the site of nerve injury facilitates superior muscle reinnervation and function. GDNF is upregulated in SCs in the distal nerve stump and skeletal muscle after injury (Nagano and Suzuki, 2003;Zhao et al, 2004) and regulates presynaptic differentiation and neuromuscular junction connections (Nagano and Suzuki, 2003;Yang and Nelson, 2004). Exogenous delivery of GDNF from NGCs at the site of injury may therefore amplify the existing endogenous mechanism of motor nerve regeneration, resulting in the improved functional reinnervation of distal musculature.…”

Early sensory protection in reverse end-to-side neurorrhaphy to improve the functional recovery of chronically denervated muscle in rat: a pilot study

“…13 Foreign axons may support denervated muscle fibers directly, by supplying trophic factors or, indirectly, by promoting repair of the endoneurial sheath, thus enhancing the regeneration of the native nerve. 22,25 Timely reinnervation induces Schwann cell proliferation 20 and the expression of neurotrophic factors such as NGF, BDNF, GDNF, and pleiotrophin, their receptors, and also neuregulin and the cognate receptor. 10,24 All of these factors, which are associated with neuronal survival and axonal growth in the peripheral nervous system, may promote the reestablishment of a functional connection at the neuromuscular junction.…”

The Pros and Cons of Growth Factors and Cytokines in Peripheral Axon Regeneration

“…Hence, any form of artificially excited muscular activity may inhibit the bridge formation by TSC and reduce postlesional intramuscular sprouting. Considering the molecular correlates of muscle polyinnervation, it should be noted that denervated muscles have been shown to produce short-range diffusible sprouting stimuli (Slack & Pockett, 1982;Zhao, Veltri, Li, Bain, & Fahnestock, 2004). Various neurotrophic factors have been identified as possible candidate stimuli (Raivich & Makwana, 2007;Sendtner, 1998).…”