Neurotrophic factors enhance the survival of muscle fibers in EDL, but not SOL, after neonatal nerve injury

Abstract

Neonatal sciatic nerve crush results in a sustained reduction of the mass of both extensor digitorum longus (EDL) and soleus (SOL) muscles in the rat. Type IIB fibers are selectively lost from EDL. We have investigated the effects of ciliary neurotrophic factor (CNTF) combined with neurotrophin (NT)-3 or NT-4 on muscle mass, as well as the number, cross-sectional area, and distribution of muscle fiber types and the number of motor neurons innervating EDL and SOL 3 mo after transient axotomy 5 days after birth. Both NT treatments prevented the axotomy-induced loss of muscle mass in both EDL and SOL and of total number of muscle fibers in EDL but not in SOL. Although IIB fiber loss was not prevented, both NT treatments resulted in altered fiber type distribution. Both NT combinations also reduced the loss of EDL motor neurons. These data suggest that a differential distribution of NT receptors on either motor neurons or muscle fibers may lead to different levels of susceptibility to neonatal axotomy.

The denervated muscle: facts and hypotheses. A historical review

“…According to Helgren et al (1994) CNTF reduces muscle atrophy and contractile changes which follow denervation, exerting therefore a myotrophic eVect, which was recently (Huang et al 2002) conWrmed. It has been also reported that CNTF reduces the weight loss after neonatal nerve crush in fast but not in slow muscles (Mousavi et al 2002) and prevents the unweighting-induced atrophy and functional changes in a postural, slow muscle such as rat soleus muscle (Fraysse et al 2000), as well as the unweighting-induced increase of CNTF receptor expression in the same muscle (Fraysse et al 2000;Guillet et al 1998). Regenerating muscles also express receptors for CNTF (Kami et al 2000), and in mice the factor accelerates myotube diVerentiation during regeneration (Marques and Neto 1997).…”

Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus

“…Third, NT-4/5 synthesis by muscle fibers is modulated by electrically evoked muscle activity in a dose-dependent manner (Funakoshi et al, 1995). Finally, the fact that treatment with ciliary neurotrophic factor (CNTF) + NT-4/5, but not with CNTF + NT-3, attenuates the reduction of the proportion of slow fibers that occurs in the rat SOL after sciatic nerve crush (Mousavi et al, 2002) provides additional support that this neurotrophin is involved in the determination of the slow muscle phenotype in the rat SOL.…”

Strategies to Reduce Age-Related Skeletal Muscle Wasting

“…CNTF participates in the survival of motor neurons and reduces denervation atrophy of skeletal muscles. 42 In preliminary experiments in old rats, CNTF levels were restored by exogenous CNTF administration, and a strong correlation was found between CNTF production and muscle performance. 37 Follow-up studies in rats 43 and humans 38 support the notion of a strong relationship between CNTF and age-related changes in muscle mass and function.…”