title: Modulation of muscle spindle innervation by neurotrophin-3 following nerve injury.
abstract: Muscle spindles monitor changes in muscle length and are innervated by groups Ia and II sensory axons as well as gamma motor axons. Ia sensory axons respond to neurotrophin-3 (NT-3), which plays an important role in sculpting proprioceptive development. Previously, transgenic mice were generated that overexpress NT-3 in muscle (mlc/NT-3 mice). These mice have alterations in proprioceptive elements due to the developmental actions of NT-3 and neuroprotective effects on Ia axons following nerve injury (Taylor, M.D., Vancura, R., Williams, J.M., Riekhof, J.T., Taylor, B.K., Wright, D.E., 2001. Overexpression of neurotrophin-3 in skeletal muscle alters normal and injury-induced limb control. Somatosens. Motor Res. 18 (4), 286-294.) Here, we investigated the actions of NT-3 on each class of injured axons innervating spindles and explored the mechanisms by which NT-3 acts. Immunohistochemical assessment of muscle spindle innervation following crush revealed that the degeneration of Ia axons innervating spindles in mlc/NT-3 mice was substantially reduced, and overall spindle innervation by group II and gamma fibers was greatly improved at later stages. Mlc/NT-3 mice also displayed a significant reduction in the expression of the injury-induced transcription factor ATF3 by retrogradely labeled muscle afferent neurons. The effects of transgenic NT-3 overexpression on spindle innervation could be mimicked if wild-type mice were treated intramuscularly with recombinant NT-3 prior to but not following injury, suggesting that NT-3's actions were due to preexposure to NT-3. This view was supported by in vitro experiments in which large DRG neurons from mlc/NT-3 mice grew significantly longer neurites than wild-type neurons. The results reveal that improved Ia-spindle interactions after injury may enhance spindle innervation by group II and gamma fibers. Finally, exposure of muscle afferent fibers to NT-3 prior to injury alters axonal responses both in vitro and in vivo.
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Angela S
authors.initials: AS
authors.lastname: Holdeman
authors.forename: Simeon G
authors.initials: SG
authors.lastname: Weltmer
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Ryals
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Wright
mesh_terms: D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009470:Muscle Spindles / Q000187:drug effects / Q000378:metabolism*; D009409:Nerve Crush / Q000379:methods; D020933:Neurotrophin 3 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
chemical_list: D020933:Neurotrophin 3