title: Impaired Axonal Regeneration in Diabetes. Perspective on the Underlying Mechanism fromIn VivoandIn VitroExperimental Studies.
abstract: Axonal regeneration after peripheral nerve injury is impaired in diabetes, but its precise mechanisms have not been elucidated. In this paper, we summarize the progress of research on altered axonal regeneration in animal models of diabetes and cultured nerve tissues exposed to hyperglycemia. Impaired nerve regeneration in animal diabetes can be attributed to dysfunction of neurons and Schwann cells, unfavorable stromal environment supportive of regenerating axons, and alterations of target tissues receptive to reinnervation. In particular, there are a number of factors such as enhanced activity of the negative regulators of axonal regeneration (e.g., phosphatase and tensin homolog deleted on chromosome 10 and Rho/Rho kinase), delayed Wallerian degeneration, alterations of the extracellular matrix components, enhanced binding of advanced glycation endproducts (AGEs) with the receptor for AGE, and delayed muscle reinnervation that can be obstacles to functional recovery after an axonal injury. It is also noteworthy that we and others have observed excessive neurite outgrowth from peripheral sensory ganglion explants from streptozotocin (STZ)-diabetic mice in culture and enhanced regeneration of small nerve fibers after sciatic nerve injury in STZ-induced diabetic rats. The excess of abortive neurite outgrowth may lead to misconnections of axons and target organs, which may interfere with appropriate target reinnervation and functional repair. Amelioration of perturbed nerve regeneration may be crucial for the future management of diabetic neuropathy.
authors.affiliation: Diabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science , Tokyo , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sango
authors.affiliation: Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine , Hirosaki , Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: TechnoMaster Co. Ltd. , Yokohama , Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Horie
authors.affiliation: Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine , Hirosaki , Japan.
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
keywords: Schwann cells; animal models; axonal regeneration; diabetic neuropathy; dorsal root ganglia