Neurotrophin-3 deficient Schwann cells impair nerve regeneration.
Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell (SC) survival and differentiation in the absence of axons. Prior studies have failed to define the explicit role of SC versus axon in NT-3 deficiency in relation to nerve regeneration and associated remyelination. In the paradigm we studied, using NT-3 heterozygous (NT3(+/-)) knockout mice capable of survival into adult-life, the experimental design provided a model uniquely capable of differentiating SC/axon influences. In these studies we first identified a defect in nerve regeneration characterized by fewer SCs in the regenerating nerve fibers of crushed sciatic nerves of NT3(+/-) mice. Subsequent experiments differentiated SC versus axonal influences as the culprit in defective nerve regeneration using sciatic nerve transplant paradigms. Results show an impairment in nerve regeneration in NT3(+/-) mice with a retardation of the myelination process, and this defect is associated with decreased SC survival and an increase in the neurofilament packing density of regenerating axons. These observations indicate that NT3(+/-) status of the SCs, but not of the axons, is responsible for impaired nerve regeneration and that NT-3 is essential for SC survival in early stages of regeneration-associated myelination in the adult peripheral nerve.
Sahenk
Zarife
Z
Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, USA. sahenk.1@osu.edu
Oblinger
Janet
J
Edwards
Chris
C
D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D009409:Nerve Crush / Q000379:methods; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D020933:Neurotrophin 3 / Q000172:deficiency*; D012583:Schwann Cells / Q000473:pathology*; D020426:Sciatic Neuropathy / Q000473:pathology* / Q000503:physiopathology*
D020933:Neurotrophin 3