title: Recovery of whisking function after manual stimulation of denervated vibrissal muscles requires brain-derived neurotrophic factor and its receptor tyrosine kinase B.
abstract: 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.
authors.affiliation: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Söhnchen
authors.forename: M
authors.initials: M
authors.lastname: Grosheva
authors.forename: S
authors.initials: S
authors.lastname: Kiryakova
authors.forename: C U
authors.initials: CU
authors.lastname: Hübbers
authors.forename: N
authors.initials: N
authors.lastname: Sinis
authors.forename: E
authors.initials: E
authors.lastname: Skouras
authors.forename: J
authors.initials: J
authors.lastname: Ankerne
authors.forename: K
authors.initials: K
authors.lastname: Kaidoglou
authors.forename: J W U
authors.initials: JW
authors.lastname: Fries
authors.forename: A
authors.initials: A
authors.lastname: Irintchev
authors.forename: S A
authors.initials: SA
authors.lastname: Dunlop
authors.forename: D N
authors.initials: DN
authors.lastname: Angelov
mesh_terms: 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*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB