Transthyretin enhances nerve regeneration.
Mutations in transthyretin (TTR) are associated with familial amyloid polyneuropathy, a neurodegenerative disorder characterized by TTR deposition in the PNS. The aim of this study was to unravel whether TTR has a role in nerve physiology that could account for its preferential accumulation in the PNS, when mutated. The sensorimotor performance of wild-type and TTR knockout (KO) littermate mice was compared and showed impairment in mice lacking TTR. Given the possibility that, upon regeneration, the consequences arising from TTR absence might be exacerbated, nerve crush was performed in both strains. TTR KO mice presented delayed functional recovery resulting from decreased number of myelinated and unmyelinated fibers. Moreover, in transgenic mice in a TTR KO background, expressing human TTR in neurons, this phenotype was rescued, reinforcing that TTR enhances nerve regeneration. In vitro assays showed that neurite outgrowth and extension were decreased in the absence of TTR, probably underlying the decreased number of regenerating axons in TTR KO mice. Our findings demonstrate that TTR participates in nerve physiology and that it enhances nerve regeneration. Moreover, the assignment of a TTR function in nerve biology and repair, may explain its preferential deposition, when mutated, in the PNS of familial amyloid polyneuropathy patients.
Fleming
Carolina E
CE
Instituto de Biologia Molecular e Celular--IBMC, Molecular Neurobiology Group, Porto, Portugal.
Saraiva
Maria J
MJ
Sousa
Mónica M
MM
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002531:Cerebellum / Q000473:pathology; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009409:Nerve Crush; D009412:Nerve Fibers / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000502:physiology; D016716:PC12 Cells; D011228:Prealbumin / Q000235:genetics / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D012584:Sciatic Nerve / Q000473:pathology / Q000502:physiology
D011228:Prealbumin