Delayed Wallerian degeneration and increased neurofilament phosphorylation in sciatic nerves of rats with streptozocin-induced diabetes. 1998

M Terada, and H Yasuda, and R Kikkawa
Third Department of Medicine, Shiga University of Medical Science, Otsu, Japan.

It is known that Wallerian degeneration (WD) is prerequisite for nerve regeneration, which is impaired in experimental diabetic rats. To elucidate the effect of hyperglycemia on WD, we studied the time course of WD after axotomy in streptozocin-diabetic (DM) and control rats. Sciatic nerves were removed at several time points after axotomy (days 0-24). Morphometric analysis indicated that WD was delayed in DM throughout experimental period. Quantitative immunohistochemical analysis showed that the early recruitment of macrophage did not differ between the two groups, although its late recruitment was significantly decreased in DM at 15 and 24 days post-axotomy, which suggested that the macrophage-associated process did not contribute to delayed WD in diabetes. Immunoblot analysis showed a delay in the degradation of neurofilaments (NFs) in DM during WD. Phosphorylated NFs detected by SMI31 were more recognized in DM, while the opposite was true for unphosphorylated NFs detected by SMI32. Since it is known that the sensitivity of NF to calpain-mediated proteolysis is modulated by its carboxyl-terminal phosphorylation state and phosphorylated NFs are resistant to calpains, we concluded that abnormal NF phosphorylation state in diabetes could be one of the mechanisms by which axonal degeneration was delayed.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297 Male Males
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012584 Sciatic Nerve A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE. Nerve, Sciatic,Nerves, Sciatic,Sciatic Nerves
D014855 Wallerian Degeneration Degeneration of distal aspects of a nerve axon following injury to the cell body or proximal portion of the axon. The process is characterized by fragmentation of the axon and its MYELIN SHEATH. Degeneration, Wallerian
D016900 Neurofilament Proteins Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302) Neurofilament Protein,Heavy Neurofilament Protein,Neurofilament Triplet Proteins,Neurofilament Protein, Heavy,Protein, Heavy Neurofilament,Protein, Neurofilament,Proteins, Neurofilament,Proteins, Neurofilament Triplet,Triplet Proteins, Neurofilament
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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