gms | German Medical Science

Objective: Recently, we showed that manual stimulation (MS) of denervated vibrissal muscles enhanced functional recovery following facial nerve cut and suture (FFA) by reducing poly-innervation at the neuro-muscular junctions (NMJ). Although the cellular correlates of poly-innervation are established, with terminal Schwann cells (TSC) processes attracting axon sprouts to “bridge” adjacent NMJ, molecular correlates are poorly understood.

Methods: Quantitative RT-PCR revealed a rapid increase of IGF-1 mRNA in denervated muscles and we examined the effect of daily MS for 2 months after FFA in IGF-1+/- heterozygous mice; controls were wild-type (WT) littermates. We quantified vibrissal motor performance and percentage of NMJ bridged by S100-positive TSC.

Results and conclusions: There were no differences between intact WT and IGF-1+/- mice for vibrissal whisking amplitude (48o and 49o) or the percentage of bridged NMJ (0%). After FFA and handling alone (i.e. no MS) in WT animals, vibrissal whisking amplitude was reduced (60% lower than intact) and the percentage of bridged NMJ increased (42% more than intact). MS improved both the amplitude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (12% more than intact). After FFA and handling in IGF-1+/- mice, the pattern was similar (whisking amplitude 57% lower than intact; proportion of bridged NMJ 42% more than intact). However, MS did not improve outcome (whisking amplitude 47% lower than intact; proportion of bridged NMJ 40% more than intact).

We conclude that IGF-I is required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function.