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P Sidenius

Publications and source records attributed to P Sidenius.

35 records · Page 2Linked to original sources
PubMed1983

Axonal transport in neuropathy.

Recent studies on the distribution of labeled endogenous proteins in the experimental neuropathies induced by streoptozotocin diabetes, galactose feeding, zinc pyridinethione, 2,5-hexanedione, acrylamide, and p-bromophenylacetylurea (BPAU) have demonstrated an impaired build up of retrogradely transported material derived from the more distal parts of peripheral nerve. In BPAU neuropathy the transport abnormality is strongly related to the degree of muscle weakness; following treatment with acrylamide the extent of the impairment is dose related. In both toxic conditions the transport abnormality is present well in advance of the first clinical signs of neuropathy. We therefore suggest that changes in retrograde axonal transport play an initial and important role in the development of many axonopathies.

Acrylamide↗
PubMed1983

Early and dose-dependent decrease of retrograde axonal transport in acrylamide-intoxicated rats.

The effect of retrograde axonal transport of doses of acrylamide ranging from 50 to 500 mg/kg was studied in sensory nerve of rats. Accumulation of trichloroacetic acid-phosphotungstic acid-insoluble label was measured in a collection segment distal to a double ligature placed on the sciatic nerve at intervals 9-15 h and 9-24 h following injection into the dorsal root ganglion of the fifth lumbar root of [35S]methionine and [3H]fucose. After a dose of 100 mg/kg of acrylamide no neurological signs of neuropathy had yet appeared, but retrograde buildup of protein label was significantly reduced for the long interval (2.20 +/- 0.49 arbitrary units (AU) (mean +/- SD) versus 2.81 +/- 0.57 AU in controls, 2p = 0.034). No abnormality of the short interval appeared before a dose of 500 mg/kg was reached. The retrograde transport abnormality was dose-related (r = -0.85, n = 28, and 2p = 1.2 x 10(-8)), as was the degree of neuropathy evaluated by "blind" neurological scoring (r = 0.88, n = 14, and 2p = 2.8 x 10(-5)). After a dose of 500 mg/kg, when the rats were severely disabled with almost total incoordination of the hindlegs, the retrograde accumulation of the long interval was profoundly depressed (1.08 +/- 0.28 AU versus 2.81 +/- 0.57 AU in controls, 2p = 1.2 x 10(-7)). Similar changes were seen in accumulation of glycoprotein label. After the rats had recovered for 4-10 weeks neurological signs of neuropathy had disappeared and the transport abnormality had improved. To test the specificity of acrylamide on the retrograde transport defect N-hydroxymethylacrylamide and methylene-bisacrylamide, which do not induce neuropathy, were studied. None of these related compounds influenced the transport. These observations imply that in acrylamide intoxication a defect in the amount of material carried by retrograde axonal transport rather than in "turnaround" time or in transport velocity is present, that the transport abnormality precedes the development of neuropathy, and that it is related to the degree of the neurological disability. We suggest that the retention of protein in the distal axons in the functional counterpart of the well-known accumulation of vesicular organelles in the preterminals.

Acrylamide↗
PubMed1983

Peripheral neuropathy in rats induced by insulin treatment.

The effect of sustained insulin-induced hypoglycemia on peripheral nerve function and structure was examined in rats. After a period of hypoglycemia (less than 2.5 mmol/L) of at least 72 h, axonal degeneration and reduction of the maximal amplitude of the evoked muscle action potential occurred, the two abnormalities being correlated negatively (r = -0.99, 2P = 0.00097). One of five rats developed paresis of both hindlegs as well as nerve damage and perikaryal alterations of lower motor neurons.

Animals↗
PubMed1982

Change in mast cell dimensions increases the profile number in sections of peripheral nerve of diabetic rats.

Mast cell proliferation has been reported in peripheral nerves of streptozotocin diabetic rats. We examined the question by light microscopy using morphometric techniques including estimation of shape and size. After 4 weeks of diabetes the mast cell area in transverse sections was 32.7 +/- 7.0 microns 2 vs. 22.5 +/- 5.4 microns 2 in controls (P less than 10(2)). Mast cell profiles approximated to ellipses in longitudinal sections, the long diameter being 11.4 +/- 1.2 microns vs. 14.0 +/- 1.0 microns in controls (P less than 10(4)). Correspondingly, the profile number was increased (30 +/- 6%) in longitudinal sections and decreased in transverse sections (11 +/- 16%). The present study does not provide evidence for mast cell proliferation in peripheral nerves in experimental diabetes, and, furthermore, underlines the need of evaluation of dimensions in studies of particle numbers.

Animals↗
PubMed1981

Retrograde axonal transport. A possible role in the development of neuropathy.

The accumulation of 3H-fucose labelled glycoprotein and 35S-methionine labelled protein carried by the retrograde axonal transport in the sensory fibres of the sciatic nerve was examined on the day after injection of streptozotocin in rats. The accumulation of fucose-label was reduced (2.8 +/- 0.4 (SD) versus 2.1 +/- 0.5 (arbitrary units), 2p = 0.0044) indicating a decreased retrograde flux of glycoproteins. This early transport abnormality could have a key role in the development of peripheral neuropathy in diabetes.

Animals↗
PubMed1980

Impaired retrograde axonal transport from a nerve crush in streptozotocin diabetic rats.

The axonal transport of proteins in crushed nerves of streptozotocin (40 mg/kg) diabetic rats was investigated 4 weeks after induction of diabetes. 35S-methionine was used as a marker for protein and 3H-fucose as a marker for glycoprotein. The precursors were injected into the fifth lumbar spinal ganglion and the accumulation of TCA-insoluble activity proximal and distal to a sciatic nerve ligature was measured at different time intervals after application of a crush. The start of accumulation distal to the ligature was delayed by 1 hour for proteins as well as for glycoproteins. Furthermore, the total amount of accumulated protein after 19 h was decreased by 18% while the decrease was 21% for glycoprotein. By insulin treatment the differences could both be prevented and reversed after 3 days of normoglycaemia. These findings demonstrate an impaired response to a nerve crush and might be the explanation for the regenerative abnormalities of peripheral nerves in diabetes.

Animals↗
PubMed1980

Axonal transport in rats after galactose feeding.

Axonal transport was studied in galactose-fed rats. Precursors for proteins and glycoproteins were injected into the fifth lumbar spinal ganglion and retrograde axonal transport as well as slow axonal transport were estimated at different time intervals during the following 4 weeks. Galactose-feeding was found to produce a progressive reduction of the retrograde axonal transport of glycoproteins in intact nerve (2.9 +/- 0.2 (arbitrary units) after five days of galactose-feeding as compared to 1.9 +/- 0.7 after 28 days, 2p = 0.025). The slow axonal transport velocity of structural proteins was reduced from 0.97 +/- 0.09 mm/day to 0.84 +/- 0.04 mm/day, 2p = 0.0030. The present findings as well as structural and electrophysiological abnormalities of the nerves of galactose-fed rats are similar to the changes found in diabetic rats. The similarities point to a decisive role for glucose or its metabolites in the development of diabetic neuropathy.

Animals↗
PubMed1980

Decreased axonal transport of structural proteins in streptozotocin diabetic rats.

We have examined the various axonal transport rates in sciatic nerve of streptozotocin diabetic rats 3 h and 10,25, and 50 d after the injection of tritiated proline into the fifth lumbar dorsal root ganglion. Proline-labeled proteins conveyed by the slow transport system were advanced more slowly in diabetic rats. No compensation for this delay took place in terms of protein synthesis, half-life, or transported amount. The decreased deliverance of slowly transported proteins (structural proteins) to the axons may well account for the reduced axon calibre shown in earlier reports. A hypothesis is proposed suggesting that the primary event in the development of neurological abnormalities in diabetes is an impairment of the retrograde axonal transport, secondarily leading to the abnormality of the anterograde transport of structural proteins.

Animals↗
PubMed1980

Reduced perikaryal volume of lower motor and primary sensory neurons in early experimental diabetes.

The volume of nerve cell bodies of the anterior horn of the fifth lumbar segment and of the fifth lumbar dorsal root ganglion were measured by stereological methods in rats with 4-wk duration of streptozotocin diabetes and in age-matched controls. The perikaryal volume of motor and sensory neurons was reduced by 18% in diabetic rats and a shift between the number of A- and B-cells was observed in the dorsal root ganglion. The findings are in accordance with our earlier observation of reduced axonal size of myelinated fibers in the common peroneal nerve. Furthermore, the data lead us to suppose that the nervous system abnormalities in early diabetes are not exclusively restricted to the peripheral nerves.

Animals↗
PubMed1980

Nervous system abnormality and nervous disease in diabetes.

Symptomatic diabetic neuropathy is present only in a few percent of the total diabetic population. In contrast abnormalities of the various parts of the nervous system can be demonstrated very early using neurophysiological techniques. These abnormalities are reversible at first, but progressive with duration of diabetes. Similar nervous abnormalities are present in experimental diabetes in the rat. The earliest structural changes have been demonstrated to be a decreased calibre of the myelinated axons. An abnormality in the axonal transport of proteins is possibly the very first change to appear. These recent results have enabled us to propose a hypothesis concerning the sequence of events in the development of the peripheral nerve abnormalities.

Animals↗
PubMed1979

Axonal transport in early experimental diabetes.

In the present study fast axonal transport was examined in streptozotocin rats with 4 weeks duration in diabetes. Tritiated leucine and 14C-labelled glucosamine were injected into the fifth lumbar ganglion and TCA-soluble as well as insoluble activity were measured in segments of the sciatic nerve at various time intervals. (1) Time from injection until start of fast axonal transport was prolonged in diabetic rats whereas anterograde transport velocity was unchanged. (2) Incorporation of labelled leucine was reduced by 40%, whereas labelled glucosamine incorporation was unchanged. (3) Alterations observed in accumulations of labelled glycoconjugates proximal and distal to a collection crush might represent a decreased amount of retrograde transported material. The changes found in protein and glycoconjugate synthesis and transport could be related to the early reduction in axon calibre and conduction velocity in peripheral nerve of streptozotocin-diabetic rat.

Animals↗
PubMedDate not supplied

No effect of growth hormone treatment on axonal transport of slow component a in diabetic and nondiabetic rats.

A decreased axonal transport of slow component a (SCa), i.e., neurofilaments, is an early event in experimental diabetes as well as hypothyroidism, and common to these metabolic derangements are decreased levels of serum insulin-like growth factor I (IGF-I). To evaluate the possible connection between these facts, we investigated the effect of growth hormone (GH), which stimulates IGF-I production, on axonal transport of SCa in diabetic and nondiabetic rats. Serum concentrations of IGF-I fell from about 1500 micrograms/L in controls to about 600 micrograms/L in diabetics. GH treatment (100 mu/rat twice daily) normalized IGF-I for the first week of diabetes, after which the level decreased to the level of the untreated diabetics. The SCa transport velocity was found to be decreased in the diabetic nerves as previously reported [0.91 +/- 0.07 = mm/day, n = 9; (mean +/- SD) versus 1.01 +/- 0.09 mm/day, n = 8, in controls, 2 p less than 0.05). No changes were seen for the GH-treated groups (1.03 +/- 0.06 mm/day, (n = 11) in GH-treated controls). The lack of effect of GH treatment can be due to blockage of IGF-I synthesis or the decreased level of thyroid hormone, triiodothyronine (T3), in the diabetic rats.

Analysis of Variance↗