title: Diabetic Schwann cells suffer from nerve growth factor and neurotrophin-3 underproduction and poor associability with axons.
abstract: Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs also provide a microenvironment favoring neural regeneration partially due to production of several neurotrophic factors. Dysfunction of SCs may also play an important role in the pathogenesis of peripheral nerve diseases such as diabetic peripheral neuropathy where hyperglycemia is often considered pathogenic. In order to study the impact of diabetes mellitus (DM) upon the regenerative capacity of adult SCs, we investigated the differential production of the neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3) by SCs harvested from the sciatic nerves of murine models of type 1 DM (streptozotocin treated C57BL/6J mice) and type 2 DM (LepR(-/-) or db/db mice) or non-diabetic cohorts. In vitro, SCs from diabetic and control mice were maintained under similar hyperglycemic and euglycemic conditions respectively. Mature SCs from diabetic mice produced lower levels of NGF and NT3 under hyperglycemic conditions when compared to SCs in euglycemia. In addition, SCs from both DM and non-DM mice appear to be incapable of insulin production, but responded to exogenous insulin with greater proliferation and heightened myelination potentiation. Moreover, SCs from diabetic animals showed poorer association with co-cultured axons. Hyperglycemia had significant impact upon SCs, potentially contributing to the pathogenesis of diabetic peripheral neuropathy.
authors.affiliation: Department of Clinical Neuroscience, Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada.
authors.forename: Indranil
authors.initials: I
authors.lastname: Dey
authors.forename: Nisha
authors.initials: N
authors.lastname: Midha
authors.forename: Geeta
authors.initials: G
authors.lastname: Singh
authors.forename: Amanda
authors.initials: A
authors.lastname: Forsyth
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Walsh
authors.forename: Bhagat
authors.initials: B
authors.lastname: Singh
authors.forename: Ranjan
authors.initials: R
authors.lastname: Kumar
authors.forename: Cory
authors.initials: C
authors.lastname: Toth
authors.forename: Rajiv
authors.initials: R
authors.lastname: Midha
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3 / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
chemical_list: D007328:Insulin; D020933:Neurotrophin 3; D020932:Nerve Growth Factor
keywords: Schwann cells; diabetic peripheral neuropathy; insulin; neurotrophins