OCCUPATIONAL NEUROPATHY: MECHANISM, DETECTION, TREATMENT

Project: Research project

Description

This is a combined experimental and clinical study of the occupational
neuropathy induced by repetitive overexposure to acrylamide monomer. The
experimental portion (90% of workload) continues from previous studies
which suggest the neuropathic potency of acrylamide is linked to toxic
inhibition of certain glycolytic enzymes which are required for the
maintenance of axonal transport and nerve-fiber integrity. Proposed
studies are designed to test this hypothesis. A tissue-culture model of
acrylamide neuropathy will be developed and used to study
acrylamide-induced degeneraion of living nerve fibers in vitro. Selected
drugs (e.g. substrates and inhibitors of glycolysis and Krebs cycle) will
be tested for their ability to modify the neurotoxic response to acrylamide
in vitro. Agents which protect by delaying or preventing the onset of
nerve-fiber degeneration in culture will be tested for their effects on
mice repeatedly treated with acrylamide. Initial studies will employ
dietary supplementation with sodium pyruvate, an effective therapeutic
regimen in rats treated with acrylamide. Treated and control animals will
be assayed for neuropathy by quantitative functional, morphological and
biochemical assays. The relationship between molecular and cellular
mechanisms of acrylamide neurotoxicity will be examined by determining the
effects of single and multiple doses on energy-dependent axonal transport.
Dose dependent decrements in fast retrograde axonal transport will be
examined in sensory and motor axons and their relationship to changes in
fast anterograde transport and distal axonal degeneration determined. The
fate of vulnerable glycolytic enzymes transported slowly from neuronal
perikaryon to nerve terminal will be examined in the optic nerves of
rabbits with advanced acrylamide neuropathy. Finally, studies in rats will
examine the current hypothesis that acrylamide induces damages to axons by
direct toxic action on nerve fibers. Rates of binding of acrylamide to
proteins in peripheral nerves will be determined with the aid of
radiolabeled toxin. The clinical portion (10% of workload) will explore
the efficacy of the newly developed Optecon Tactile Tester to monitor
worker populations at risk for acrylamide and related neuropathies. The
major goals of these studies are to develop experimentally proven methods
to diagnose, prevent and treat individuals with acrylamide and related
occupational neuropathies. These studies respond to some of the research
needs specified in the National Institute of Occupational Safety and Health
Criterion Document for Acrylamide (1976).
StatusFinished
Effective start/end date5/1/834/30/86

Funding

  • National Institutes of Health

Fingerprint

Acrylamide
Axonal Transport
Nerve Fibers
Workload
Axons
Toxic Actions
Citric Acid Cycle
Touch
Glycolysis
Occupational Health
Enzymes
Optic Nerve
Pyruvic Acid
Peripheral Nerves
Sodium

ASJC

  • Medicine(all)