title: Altered sciatic nerve fiber morphology and endoneural microvessels in mouse models relevant for obesity, peripheral diabetic polyneuropathy, and the metabolic syndrome.
abstract: The morphology of sciatic nerves from leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. Sciatic nerves from three groups of 4-month-old mice (WT C57BL6, ob/ob, and db/db) were investigated. In ultrathin sections, the thickness of myelin sheaths was significantly reduced in small, medium-sized, and large axons of db/db mice compared with WT mice. In ob/ob mice, only large fibers showed a decrease in myelin sheath thickness. The number of nonmyelinated nerve fibers was lower in ob/ob mice than in the db/db group. A thickened basal lamina of Schwann cells occurred in the ob/ob group only. In contrast, the basement membrane of endoneural microvessels was thickened in both obese groups. For this reason, laminin expression in Western blot analysis was lower in the db/db group than in the ob/ob one. Endoneural microvessels, which had been injected with fluorescein isothiocyanate, depicted signs of vasodilatation in the ob/ob and vasoconstriction in db/db mice. Endoneural vessels displayed two receptors of oxLDL. LOX-1 was strongly expressed in db/db mice, whereas TLR4 was at its maximum in the ob/ob group. We conclude that changes in nerve fibers and in endoneural microvessels are present in sciatic nerve of both mouse models of type 2 diabetes. Upregulation of oxLDL-dependent receptors in endoneural microvessels might be connected to different degrees of oxidative stress in severe diabetic db/db mice and in the mild diabetic ob/ob group.
authors.affiliation: Institute of Anatomy, University of Leipzig, Leipzig, Germany. marcin.nowicki@medizin.uni-leipzig.de
authors.forename: Marcin
authors.initials: M
authors.lastname: Nowicki
authors.forename: Joanna
authors.initials: J
authors.lastname: Kosacka
authors.forename: Heike
authors.initials: H
authors.lastname: Serke
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Katharina
authors.initials: K
authors.lastname: Spanel-Borowski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001485:Basement Membrane / Q000473:pathology / Q000648:ultrastructure; D001835:Body Weight / Q000235:genetics; D018955:CD36 Antigens / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D007797:Laminin / Q000378:metabolism; D020738:Leptin / Q000172:deficiency; D024821:Metabolic Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000473:pathology* / Q000648:ultrastructure; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D054411:Receptors, Leptin / Q000172:deficiency; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D012583:Schwann Cells; D012584:Sciatic Nerve / Q000473:pathology* / Q000648:ultrastructure; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014841:von Willebrand Factor
chemical_list: D018955:CD36 Antigens; D007797:Laminin; D020738:Leptin; C495138:Olr1 protein, mouse; D054411:Receptors, Leptin; D051127:Scavenger Receptors, Class E; D017392:Thiobarbituric Acid Reactive Substances; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C515447:leptin receptor, mouse; D014841:von Willebrand Factor