Peripheral Neuropathy in Rats Produced by Acrylamide

Fullerton, Pamela M.; Barnes, J. M.

doi:10.1136/oem.23.3.210

Cited by 136 publications

(100 citation statements)

References 13 publications

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“…Acrylamide ingestion robustly causes a retrograde pattern of sensorimotor axonal loss in rodents, and we and others have previously shown that the extent of this distal axonal loss closely correlates with the severity of hind limb grip weakness (4,21,23,27). In subsequent ex vivo experiments, we noted that relatively low doses of the NO donors SNAP and NOR3 prevented axonal degeneration in DRG cultures induced by acrylamide.…”

Section: Discussionmentioning

confidence: 87%

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Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Keswani

Bosch–Marcé

Reed

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Nitric oxide (NO) is a signaling molecule that can trigger adaptive (physiological) or maladaptive (pathological) responses to stress stimuli in a context-dependent manner. We have previously reported that NO may signal axonal injury to neighboring glial cells. In this study, we show that mice deficient in neuronal nitric oxide synthase (nNOS −/− ) are more vulnerable than WT mice to toxin-induced peripheral neuropathy. The administration of NO donors to primary dorsal root ganglion cultures prevents axonal degeneration induced by acrylamide in a dose-dependent manner. We demonstrate that NO-induced axonal protection is dependent on hypoxia-inducible factor (HIF)-1-mediated transcription of erythropoietin (EPO) within glial (Schwann) cells present in the cultures. Transduction of Schwann cells with adenovirus AdCA5 encoding a constitutively active form of HIF-1α results in amelioration of acrylamide-induced axonal degeneration in an EPOdependent manner. Mice that are partially deficient in HIF-1α (HIF-1α +/− ) are also more susceptible than WT littermates to toxic neuropathy. Our results indicate that NO→HIF-1→EPO signaling represents an adaptive mechanism that protects against axonal degeneration.

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Section: Discussionmentioning

confidence: 87%

“…Acrylamide-induced peripheral neuropathy is a well-established, reproducible rodent model of distal axonal degeneration (21). Acrylamide is known to interfere with slow axonal transport (22).…”

Section: Resultsmentioning

confidence: 99%

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Keswani

Bosch–Marcé

Reed

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This chemical appears to damage nerve tissue selectively and has been known for some time to cause peripheral neuropathies (Fullerton and Barnes, 1966;Pleasure et al, 1970;Schaumberg et al, 1974). More recently central nervous system involvement in acrylamide poisoning has also been reported in experimental animals (Ghetti et al, 1973;Gipon et al, 1977;Schotman et al, 1978;Schaumburg and Spencer, 1978).…”

mentioning

confidence: 99%

“…These include pupil dilation, excess salivation, distension of the urinary bladder, and tremor (Fullerton and Barnes, 1966;Thoman et al, 1974).…”

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confidence: 99%

The effects of acrylamide treatment upon the dopamine receptor

Agrawal

Squibb

Bondy

1981

Toxicology and Applied Pharmacology

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. (1981). Toxicol. Appl. Pharmacol. 58,[89][90][91][92][93][94][95][96][97][98][99]. The binding of tritiated spiroperidol to striatal membranes prepared from acrylamide-treated male 6-week-old rats and matched controls has been studied. This binding has highaffinity characteristics and is stereospecific and reversible. Equilibrium was attained within 15 min at 37°C. The extent of binding was much more pronounced in the striatum than in any other brain region and was not detectable within the cerebellum or spinal cord. Regional distribution of binding and competition studies with other pharmacologic agents suggested a correspondence between the location of ligand-membrane complex formation and the dopamine receptor. Twenty-four hours after a single oral administration of acrylamide there was a significant increase in [ 3 H]spiroperidol binding at all acrylamide doses tested (50, 100, and 200 mJYkg body weight). However, there was no significant change in striatal dopamine levels of treated animals. Kinetic analysis of animals treated with 100 mg acrylamide/kg suggested increased affinity of receptors of treated animals toward the labeled ligand. Receptor densicy was only slightly elevated in experimental animals. Effects were also studied in rats that had received 10, 20, or 30 mg/kg acrylamide daily for 10 days. Twentyfour hours after the last dose there was a major increase in spiroperidol binding in treated animals. Scatchard plot analysis again revealed that this change was largely attributable to a change in the dissociation constant of the binding interaction but also there was an increase in the overall number of receptor sites. Nonna! values were restored within 8 days after cessation of dosing. This illustrates that, under the conditions of this experiment, the effect of acrylamide on a central neurotransmitter system is reversible.

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“…The peripheral nervous system is clearly damaged and both human and experimentally-induced neuropathies have been described (Tilson et al 1979;Fullerton and Barnes 1966;Fujita et al 1961). Central nervous system malfunction is also reported for experimental animals and humans (Igisu et al 1975;Spencer and Schaumburg 1974).…”

Section: Introductionmentioning

confidence: 99%

Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones

et al. 1983

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Abstract. The effect of acute and subchronic acrylamide treatment on levels of dopamine, serotonin, and their metabolites was determined in several brain regions of the rat. Concentrations of several neuropeptides and circulating hormones were also measured. Both a single and repeated doses of acrylamide resulted in elevated levels of 5-hydroxyindolacetic acid in all regions studied (frontal cortex, striatum, hippocampus, brain stem, and hypothalamus). Changes in regional content of other monoamines were much less pronounced. Turnover studies following pargyline blockage of monoamine oxidase, suggested results were due to increased rates of serotonin turnover in acrylamide-treated rats.Changes in neuropeptide levels were only detected in the hypothalamus where a single acrylamide treatment caused elevated levels of fi-endorphin and substance P, and in frontal cortex where met-enkephalin levels were higher after repeated acrylamide injection. Such repeated injection caused a major depression in plasma levels of testosterone and prolactin.

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Peripheral Neuropathy in Rats Produced by Acrylamide

Cited by 136 publications

References 13 publications

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin

The effects of acrylamide treatment upon the dopamine receptor

Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones

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