TY - JOUR
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
N1 - Funding Information:
The authors are grateful to Drs. Louis F. Reichardt (University of California, San Francisco) and Martin Korte (Max-Planck-Institute for Neurobiology, Martinsried) for BDNF and TrkB-deficient mice, to Drs. Udo Bartsch and Maren von der Ohe for many helpful discussions, Emanuela Szpotowicz and Neil Tyreman for technical assistance, and the Roechling and Hertie Foundations, Erika and Condrad W. Schnyder-Stiftung, the Deutsche Forschungsgemeinschaft (Scha 185/28-1,2 to M. S.), the Canadian Institutes of Health Research (CIHR cg 37534 to T. G.) and the National Institutes of Health (NIH RO1 NS034484-8 to T.M.B.) for support.
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 - BDNF
KW - Femoral nerve
KW - HNK-1 carbohydrate
KW - Motion analysis
KW - Motoneuron
KW - Mouse
KW - Regeneration
KW - TrkB
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U2 - 10.1016/j.expneurol.2005.12.018
DO - 10.1016/j.expneurol.2005.12.018
M3 - Article
C2 - 16460731
AN - SCOPUS:33645741487
SN - 0014-4886
VL - 198
SP - 500
EP - 510
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -