Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies?
Spencer PS; Sabri MI; Schaumburg HH; Moore CL
Ann Neurol 1979 Jun; 5(6):501-507
The patterns of distal symmetrical polyneuropathy produced in humans and animals by a several chemically unrelated neurotoxins and various metabolic abnormalities and categorized as central peripheral distal axonopathy were reviewed with regard to determination of an underlying mechanism. Studies focused on industrial outbreaks of human disease following exposure to hexacarbon solvents, childhood giant axonal neuropathy associated with abnormal hair, and laboratory models induced by methyl-n-butyl- ketone (591786) and n-hexane (110543). The pathology of the diseases was characterized by mixed neuropathy affecting primarily motor fibers with axonal degeneration demarcated by giant distal axonal swellings. Axonal transport studies indicated that the nerve fiber locus of toxic damage was an impairment of the axonal transport of perikaryal materials necessary for the maintenance of axonal integrity. Giant axonal swellings from beta,beta'- iminodipropionitrile (111944) intoxication and hexacarbon treatment contained 10 nanometer neurofilaments resulting from a selective blockade of the slow phase of axonal transport. A potential relationship between energy deprivation within the axon, changes in conduction velocity, and the accumulation of transported materials was suggested by the inhibition of glyceraldehyde-3-phosphate- dehydrogenase activity by methyl-n-butylketone, 2,5-hexanedione (110134), acrylamide (79061), and carbon-disulfide (75150). The authors hypothesize that the failure of an adequate supply of glucolytic enzymes arriving in the distal axon induces axonal transport difficulties resulting in the accumulation of neurofilaments associated with axonal degeneration and clinical neuropathy.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Histopathology; Enzymatic-effects; Peripheral-nervous-system; Central-nervous-system; Nerve-fibers; Neuromotor-system-disorders; Organic-solvents
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
591-78-6; 110-54-3; 111-94-4; 110-13-4; 79-06-1; 75-15-0
Neurotoxic Disorders; Neurotoxic-effects
Annals of Neurology
Yeshiva University, New York, New York