• LoPachin, Richard M. (PI)
  • LoPachin, Richard M. (PI)
  • Rose, Susan A. (PI)
  • Rose, Susan A. (PI)

Project: Research project

Project Details


Chronic exposure to acrylamide causes skeletal muscle weakness associated
with a distal axonopathy. The biochemical lesion responsible for this
neuronal damage has not been identified. Recent research indicates that an
increase in intraneuronal calcium induced by a variety of injurious
processes (e.g. chemical, disease) is responsible for the resulting
neuronal damage and/or death. Thus, acrylamide might produce injury by
causing cellular membranes to become "leaky" thereby allowing an influx of
extracellular calcium and other ions. The resulting increase in
cytoplasmic calcium could cause nerve cell injury by inhibiting
mitochondrial respiration, by disrupting cytoskeletal structure or by a
direct inhibition of axonal transport. The proposed investigation will
determine whether a progressive increase in the concentration of calcium is
temporally related to acrylamide intoxication. These studies will involve
the use of nervous tissues from acrylamide-treated rats and nerve cell
culture systems exposed to this neurotoxin. Specifically, initial studies
will employ atomic absorption spectrophotometry to measure
acrylamide-induced changes in total calcium concentrations. Changes in
calcium levels will be correlated temporally with the development of
neuronal damage caused by acrylamide. Autoradiography (45Ca) will be used
to identify nuclei or regions in brains from acrylamide-treated rats which
exhibit changes in calcium uptake and/or retention. Such areas (e.g.
cerebellum) might represent structures which are selectively damaged by
acrylamide and therefore are importantly involved in the manifestation of
neurotoxicity. Alterations in the subcellular distribution of calcium and
other ions produced by acrylamide will be determined using x-ray
microanalysis. With this technique it is possible to measure ion
concentrations in mitochondria and other subcellular organelle. Acrylamide
neurotoxicity might be mediated by the inhibitory effect of calcium on
mitochondrial respiration. Therefore, oxygen uptake will be measured using
a Clark's oxygen electrode in nervous tissues and in nerve cell cultures
exposed to acrylamide. The long range goal of this research is to identify
the role of calcium in the distal axonpathy produced by acrylamide and
other neurotoxins. Results from this research might implicate an
involvement of calcium in human disease states (e.g. infantile neuroaxonal
dystrophy) which are associated with neuropathic changes similar to those
induced by acrylamide.
Effective start/end date12/31/897/31/18


  • Clinical Neurology
  • Molecular Biology
  • Spectroscopy
  • Cell Biology
  • Environmental Science(all)
  • Genetics
  • Medicine(all)
  • Toxicology


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