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The influence of reduced expression of the TrkB receptor on peripheral nerve regeneration in mice
Der Einfluss einer reduzierten Expression des TrkB Rezeptors auf die periphere Nervenregeneration in Mäusen
Eberhardt, Kirsten Alexandra
Dokument 1.pdf (916 KB)
44.65 , 44.90
Schachner, Melitta (Prof. Dr.)
Tag der mündlichen Prüfung:
Kurzfassung auf Englisch:
Peripheral neurons have the ability to regenerate their axons after axotomy but functional recovery is often poor. Knowledge of cellular and molecular factors limiting or promoting restoration of function and design of efficient therapeutic approaches remain serious challenges for neuroscience and medicine.
This study was designed to analyze the influence of the TrkB receptor on peripheral nerve regeneration in vivo. Axonal regeneration and functional recovery were analyzed at different time points after transection and surgical repair of the femoral nerve in heterozygous TrkB +/- mice, animals with a reduced amount of available TrkB receptors, and in wild-type (TrkB +/+) littermates.
One month after nerve injury significantly lower numbers of myelinated axons were found in the motor branch of the femoral nerve of TrkB +/- compared with TrkB +/+ mice. This difference disappeared at three months after nerve injury, a time-point at which also axonal diameters and myelin thickness were similar in the two genotypes. Thus, although partial TrkB deficiency does not compromise axonal regeneration, leads to a delay of axonal regrowth and/or remyelination.
Retrograde labelling of regenerated motoneurons three months after injury revealed that in TrkB +/- mice more, as compared with TrkB +/+ mice, motor axons have regrown into the wrong target pathway, the saphenous nerve branch, and less have correctly reinnervated the quadriceps nerve branch of the femoral nerve. This finding shows that, in addition to delay in axonal regrowth, reduced expression of TrkB leads to reduced precision of muscle reinnervation.
Finally, functional analysis revealed gait deficits in TrkB +/- versus TrkB +/+ mice at one but not at three months after nerve injury. Thus, similar to
axonal regrowth, a reduced expression of TrkB leads to delayed functional recovery.
In summary, this work shows that TrkB signaling is a major factor regulating the axonal regrowth and precision of target reinnervation after nerve repair. Strategies leading to stimulation of TrkB signaling may be a promising way to improve the functional outcome after traumatic nerve injuries in clinical settings.