Recovery of whisking function after manual stimulation of denervated vibrissal muscles requires brain-derived neurotrophic factor and its receptor tyrosine kinase B.
Functional recovery following facial nerve injury is poor. Neuromuscular junctions (NMJs) are "bridged" by terminal Schwann cells and numerous regenerating axonal sprouts. We have shown that this poly-innervation of NMJs can be reduced by manual stimulation (MS) with restoration of whisking function. In addition, we have recently reported that insulin-like growth factor-1 (IGF-1) is required to mediate the beneficial effects of MS. Here we extend our findings to brain derived neurotrophic factor (BDNF). We then examined the effect of MS after facial-facial anastomosis (FFA) in heterozygous mice deficient in BDNF (BDNF(+/-)) or in its receptor TrkB (TrkB(+/-)). We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive terminal Schwann cells. In intact BDNF(+/-) or TrkB(+/-) mice and their wild type (WT) littermates, there were no differences in vibrissal whisking nor in the percentage of bridged NMJ (0% in each genotype). 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 (27% more than intact). MS improved both the amplitude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (11% more than intact). After FFA and handling in BDNF(+/-) or TrkB(+/-) mice, whisking amplitude was again reduced (53% and 60% lower than intact) and proportion of bridged NMJ increased (24% and 29% more than intact). However, MS failed to improve outcome in both heterozygous strains (whisking amplitude 55% and 58% lower than intact; proportion of bridged NMJ 27% and 18% more than intact). We conclude that BDNF and TRkB are required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function.
Söhnchen
J
J
Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, Germany.
Grosheva
M
M
Kiryakova
S
S
Hübbers
C U
CU
Sinis
N
N
Skouras
E
E
Ankerne
J
J
Kaidoglou
K
K
Fries
J W U
JW
Irintchev
A
A
Dunlop
S A
SA
Angelov
D N
DN
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009121:Muscle Denervation; D009416:Nerve Regeneration / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D011897:Random Allocation; D020813:Receptor, trkB / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation* / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB