title: BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair.
abstract: Functional recovery after peripheral nerve injury is often poor despite high regenerative capacity of peripheral neurons. In search for novel treatments, brief electrical stimulation of the acutely lesioned nerve has recently been identified as a clinically feasible approach increasing precision of axonal regrowth. The effects of this stimulation appear to be mediated by BDNF and its receptor, TrkB, but the down-stream effectors are unknown. A potential candidate is the HNK-1 carbohydrate known to be selectively reexpressed in motor but not sensory nerve branches of the mouse femoral nerve and to enhance growth of motor but not sensory axons in vitro. Here, we show that short-term low-frequency electrical stimulation (1 h, 20 Hz) of the lesioned and surgically repaired femoral nerve in wild-type mice causes a motor nerve-specific enhancement of HNK-1 expression correlating with previously reported acceleration of muscle reinnervation. Such enhanced HNK-1 expression was not observed after electrical stimulation in heterozygous BDNF or TrkB-deficient mice. Accordingly, the degree of proper reinnervation of the quadriceps muscle, as indicated by retrograde labeling of motoneurons, was reduced in TrkB+/- mice compared to wild-type littermates. Also, recovery of quadriceps muscle function, evaluated by a novel single-frame motion analysis approach, and axonal regrowth into the distal nerve stump, assessed morphologically, were considerably delayed in TrkB+/- mice. These findings indicate that BDNF/TrkB signaling is important for functional recovery after nerve repair and suggest that up-regulation of the HNK-1 glycan is linked to this phenomenon.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Eberhardt
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Abdulhakeem A
authors.initials: AA
authors.lastname: Al-Majed
authors.forename: Olga
authors.initials: O
authors.lastname: Simova
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Brushart
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D019771:Axotomy / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000378:metabolism*; D018959:CD57 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D005267:Femoral Nerve / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology; D020813:Receptor, trkB / Q000172:deficiency / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018959:CD57 Antigens; D020813:Receptor, trkB