Fine-structural localization of aldose reductase and ouabain-sensitive, K+-dependent p-nitro-phenylphosphatase in rat peripheral nerve

Abstract

Aldose reductase was visualized by light and electron microscopy using a goat anti-rat antibody with immunoperoxidase and immunogold, respectively. Ouabain-sensitive, K(+)-dependent, p-nitro-phenylphosphatase, a component of (Na+, K+)-ATPase, was localized at the electron microscopic level by enzyme histochemistry using p-nitro-phenylphosphate as substrate. In peripheral nerve, spinal ganglia and roots, the Schwann cell of myelinated fibers was the principal site of aldose reductase localization. Immunostaining was intense in the paranodal region and the Schmidt-Lanterman clefts as well as in cytoplasm of the terminal expansions of paranodal myelin lamellae and the nodal microvilli. Schwann cell cytoplasm of unmyelinated fibers were faintly labelled. Endoneurial vessel endothelia, pericytes and perineurium failed to bind appreciable amounts of aldose reductase antibody. However, mast cell granules bound antibody strongly. In contrast, p-nitro-phenylphosphatase reaction product was detected in the nodal axolemma, terminal loops of Schwann cell cytoplasm and the innermost layer of perineurial cells. In endothelial cells, reaction product was localized on either the luminal or abluminal, or on both luminal and abluminal plasmalemma. Endothelial vesicular profiles were often loaded with reaction product. Occasional staining of myelin and axonal organelles was noted. Mast cells lacked reaction product.

Dynorphin A, kappa opioid receptors and the antinociceptive efficacy of asimadoline in streptozotocin-induced diabetic rats

“…However, we did not detect dynorphin A in axons of diabetic rats and the cellular distribution remained restricted to non-neuronal cells. Schwann cells are the primary lesion site for many hyperglycaemia-induced nerve changes, as they contain aldose reductase [26] and it is plausible that increased dynorphin A production represents another intracellular response to increased flux through the polyol pathway, although we have yet to investigate this possibility. When considering the functional consequences of increased dynorphin A in peripheral nerve during diabetes, it is noteworthy that the increase was coincident with the presence of tactile allodynia and formalin-evoked hyperalgesia.…”

Phosphorylation of c-Jun N-terminal kinase (JNK) in sensory neurones of diabetic rats, with possible effects on nerve conduction and neuropathic pain: prevention with an aldose reductase inhibitor

“…4). This is striking because of the inhibition of JNK phosphorylation by fidarestat, an inhibitor of an enzyme thought to be primarily in the Schwann cell and not the axon [13].…”

Schwann cell interactions with axons and microvessels in diabetic neuropathy

“…Studies in which expression of enzymes involved in the polyol pathway has been manipulated have placed a particular focus on the metabolic consequences of excessive metabolism of glucose to sorbitol owing to high activity of aldose reductase [35][36][37][38] . On the basis of the involvement of the polyol pathway, the perception of diabetic neuropathy as a micro vascular complication of diabetes has been underpinned by immunocytochemical studies that showed localization of aldose reductase to the endothelial cells of epineurial and dorsal root ganglion blood vessels and to perivascular sympathetic axons [39][40][41] . Indeed, recent data implicates aldose reductase activity in the production of endothelial proinflammatory and prothrombotic signals 42 , a pathogenic cascade that is currently receiving close attention in the context of diabetic neuro pathy 42 and is discussed in detail below (see the section 'Microvascular changes in Schwann cells').…”

“…Indeed, recent data implicates aldose reductase activity in the production of endothelial proinflammatory and prothrombotic signals 42 , a pathogenic cascade that is currently receiving close attention in the context of diabetic neuro pathy 42 and is discussed in detail below (see the section 'Microvascular changes in Schwann cells'). However, within the endoneurium, aldose reductase is restricted to the myelinating Schwann cells of somatic nerves and to satellite glial cells in the dorsal root ganglia [39][40][41] …”