BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair
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BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair. / Eberhardt, Kirsten A; Irintchev, Andrey; Al-Majed, Abdulhakeem A; Simova, Olga; Brushart, Thomas M; Gordon, Tessa; Schachner, Melitta.
in: EXP NEUROL, Jahrgang 198, Nr. 2, 04.2006, S. 500-10.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair
AU - Eberhardt, Kirsten A
AU - Irintchev, Andrey
AU - Al-Majed, Abdulhakeem A
AU - Simova, Olga
AU - Brushart, Thomas M
AU - Gordon, Tessa
AU - Schachner, Melitta
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
KW - Animals
KW - Axotomy/methods
KW - Brain-Derived Neurotrophic Factor/deficiency
KW - CD57 Antigens/metabolism
KW - Disease Models, Animal
KW - Electric Stimulation/methods
KW - Femoral Nerve/cytology
KW - Gene Expression Regulation/radiation effects
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Motor Neurons/pathology
KW - Nerve Regeneration/physiology
KW - Peripheral Nerves/pathology
KW - Peripheral Nervous System Diseases/physiopathology
KW - Receptor, trkB/deficiency
KW - Recovery of Function/physiology
KW - Signal Transduction/physiology
KW - Time Factors
U2 - 10.1016/j.expneurol.2005.12.018
DO - 10.1016/j.expneurol.2005.12.018
M3 - SCORING: Journal article
C2 - 16460731
VL - 198
SP - 500
EP - 510
JO - EXP NEUROL
JF - EXP NEUROL
SN - 0014-4886
IS - 2
ER -