Recovery of whisking function after manual stimulation of denervated vibrissal muscles requires brain-derived neurotrophic factor and its receptor tyrosine kinase B

• Published in: Neuroscience Vol. 170; no. 1; pp. 372 - 380
• Main Authors: Söhnchen, J, Grosheva, M, Kiryakova, S, Hübbers, C.U, Sinis, N, Skouras, E, Ankerne, J, Kaidoglou, K, Fries, J.W.U, Irintchev, A, Dunlop, S.A, Angelov, D.N
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 29-09-2010; Elsevier
• Subjects: Anastomosis; Animals; axotomy; Biological and medical sciences; Brain-Derived Neurotrophic Factor - physiology; facial nerve; Female; Fundamental and applied biological sciences. Psychology; Mice; Mice, Transgenic; motor end-plate; Muscle Denervation; Nerve Regeneration - physiology; Neurology; Physical Stimulation - methods; polyinnervation; Random Allocation; Receptor, trkB - physiology; Recovery of Function - physiology; terminal Schwann cells; Vertebrates: nervous system and sense organs; Vibrissae - innervation; Vibrissae - physiology; motor end-plate; FFA; brain derived neurotrophic factor; facial nerve; BDNF; manual stimulation; MS; insulin-like growth factor-1; terminal Schwann cells; IGF-1; mRNA; NMJ; axotomy; tyrosine kinase B; mice; wild type(mice); TrkB; neuromuscular junction; polyinnervation; facial-facial anastomosis; WT; messenger ribonuclein acid; Neuroglia; Rodentia; Facial nerve; Stimulation; trk receptor; Vertebrata; Axotomy; Mammalia; Functional recovery; Mouse; Schwann cell; Animal; Muscle; Brain derived neurotrophic factor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.06.053

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.