Experimental vitamin E deficiency in rats. Morphological and functional evidence of abnormal axonal transport secondary to free radical damage.
Morphological and functional studies have been performed on experimental vitamin E deficient rats. The predominant morphological change was axonal dystrophy and degeneration in the rostral parts of the dorsal columns, particularly in the gracile fasciculi. The dystrophic changes comprised focal axonal swellings containing accumulations of normal and abnormal organelles which included tubulovesicular structures probably derived from the smooth endoplasmic reticulum, mitochondria, dense lamellar bodies, neurofilaments, multifascicular bodies and lysosomes. Similar but lesser changes were observed in distal peripheral nerves. The appearances suggested a disturbance of axonal transport with a defect of 'turnaround' in the distal axons. Studies on the axonal transport of endogenous acetylcholinesterase showed an impairment both of fast anterograde and retrograde transport. The changes were considered to be secondary to the lack of the antioxidant effect of vitamin E as the neurological deficits could be reduced by the concomitant dietary administration of the synthetic antioxidant ethoxyquin and were markedly aggravated by the administration of polyunsaturated fatty acids. It is suggested that the neurological syndrome produced by vitamin E deficiency could be the result of damage to the function of mitochondria and other intra-axonal membranous structures which would interfer both with fast anterograde transport and 'turnaround' and lead to a distal axonal degeneration.
Southam
E
E
Department of Neurological Science, Royal Free Hospital School of Medicine, London, UK.
Thomas
P K
PK
King
R H
RH
Goss-Sampson
M A
MA
Muller
D P
DP
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D005015:Ethoxyquin / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005609:Free Radicals; D005727:Ganglia, Spinal / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D013497:Sural Nerve / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014811:Vitamin E Deficiency / Q000473:pathology* / Q000503:physiopathology
D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D005015:Ethoxyquin; D000110:Acetylcholinesterase