Biochemical Mechanisms Underlying Primary Degeneration of Axons

Spencer, Peter S.; Miller, Matthew S.; Ross, Stephen M.; Schwab, Bradley W.; Sabri, Mohammad I.

doi:10.1007/978-1-4757-6740-7_2

Cited by 12 publications

(8 citation statements)

References 94 publications

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“…Although several investigators have suggested that deficits in axonal transport underly the pathogenesis of axonal degeneration in acrylamide neuropathy (Sabri and Spencer, 1980;Brimijoin, 1984;Spencer et al, 1985;Sickles, 1989;Sabri and Spencer, 1990;Sickles et al, 1990), the precise mechanism is unknown. The intimate relationship between fast axonal transport and microtubules is evident from studies of colchicine and vinca alkaloids, agents that disassemble microtubules, block fast axonal transport, and induce axonal degeneration (Chan et al, 1980;Ghetti et al, 1982;Dustin, 1984).…”

Section: Introductionmentioning

confidence: 99%

Effect of acrylamide on the distribution of microtubule-associated proteins (MAP1 and MAP2) in selected regions of rat brain

Chauhan

Spencer

Sabri

1993

Molecular and Chemical Neuropathology

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The effect of acrylamide treatment on the immunocytochemical localization of microtubule-associated proteins (MAP1 and MAP2) was studied in different brain regions (cerebellum, cerebral cortex, and hippocampus) of adult rats. Animals were treated with acrylamide (estimated mean dose: 15 mg/kg/d) orally for 2 wk when they showed slight hindlimb weakness. Immunoreactivity for MAP1 and MAP2 was detected in tissue sections with monoclonal antibodies according to the Sternberger's peroxidase-antiperoxidase technique. Intense MAP1 immunoreactivity was observed in neuronal perikarya and dendrites, with faint staining in axons. By contrast, MAP2 immunostaining was selectively observed in dendrites and neuronal perikarya. Treatment of animals with acrylamide reduced immunoreactivity for both MAP1 and MAP2 in hippocampus and cerebellum, with relatively little change in cerebral cortex. Loss of MAPs immunoreactivity in affected brain areas likely proceeded from dendrite to perikaryon. The results of this study indicate that hippocampal compromise is part of the neurotoxic picture associated with rodent exposure to acrylamide.

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Section: Introductionmentioning

confidence: 99%

Effect of acrylamide on the distribution of microtubule-associated proteins (MAP1 and MAP2) in selected regions of rat brain

Chauhan

Spencer

Sabri

1993

Molecular and Chemical Neuropathology

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“…Solomonson concluded that cyanide may impact the intermediary metabolism of carbohydrates with a decrease in the rate of glycolysis and the inhibition of the TCA cycle (Solomonson, 1981). Spencer and co-workers have argued that the cyanide related to tropical ataxic neuropathy is CPDA (Spencer et al, 1985). Further research on the role of cyanide in the DMAPN neurotoxicity is in progress.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of the inhibition of glycolytic enzymes by the neurotoxicant dimethylaminopropionitrile

Froines

Watson

1985

Journal of Toxicology and Environmental Health

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The neurotoxic aminonitrile dimethylaminopropionitrile (DMAPN) inhibits the crystalline glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fructose-6-phosphate kinase (phosphofructokinase, PFK). Preincubation of GAPDH with the aminonitrile enhances the inhibition, indicating that the inhibition is irreversible. The overall bimolecular rate constant ki was determined to be 2.42 +/- 0.21 M-1 min-1. Dithiothreitol (DTT) partially protected the enzyme from inhibition. PFK is also inhibited by DMAPN, but the inhibition is reversible and noncompetitive with a Kl, of 2.79 X 10(-2) M. DMAPN does not inhibit lactate dehydrogenase (LDH), nor is GAPDH or PFK inhibited by 3,3'-iminodipropionitrile (IDPN).

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“…Moreover, differences in metabolic competency between neuronal and terminal axonal mitochondria may render long axons more vulnerable to toxic-metabolic conditions compromising energy production. 15 As more patients with MSUD survive into adulthood, one may find that acute axonal neuropathy is a common sequela of long-term elevations of BCAA levels.…”

Section: Discussionmentioning

confidence: 99%