Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1).
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. Since quantitative RT-PCR revealed a rapid increase of IGF-1 mRNA in denervated muscles, we examined the effect of daily MS for 2 months after FFA in IGF-1(+/-) heterozygous mice; controls were wild-type (WT) littermates including intact animals. We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive TSC. There were no differences between intact WT and IGF-1(+/-) mice for vibrissal whisking amplitude (48 degrees and 49 degrees ) 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.
Kiryakova
S
S
Department of Anatomy I, University of Cologne, D-50924 Cologne, Germany.
Söhnchen
J
J
Grosheva
M
M
Schuetz
U
U
Marinova
Ts
Ts
Dzhupanova
R
R
Sinis
N
N
Hübbers
C U
CU
Skouras
E
E
Ankerne
J
J
Fries
J W U
JW
Irintchev
A
A
Dunlop
S A
SA
Angelov
D N
DN
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005152:Facial Muscles / Q000502:physiology*; D020220:Facial Nerve Injuries / Q000473:pathology / Q000534:rehabilitation*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006234:Handling, Psychological; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009068:Movement / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D012038:Regeneration / Q000502:physiology; D009418:S100 Proteins / Q000378:metabolism; D014738:Vibrissae / Q000294:innervation / Q000502:physiology*
D011978:Receptors, Nicotinic; D009418:S100 Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1