A Light and Electron Microscopic Histochemical Study on the Mechanism of Dfp‐induced Acute and Subacute Myopathy

Tóth, Lajos; Karcsú, Sarolta; Poberai, M; Savay, G

doi:10.1111/j.1365-2990.1981.tb00241.x

Cited by 12 publications

References 30 publications

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Morphological and electrophysiological study of distal motor nerve fiber degeneration and sprouting after irreversible cholinesterase inhibition

Kawabuchi

Cintra

Deshpande

et al. 1991

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A single subcutaneous injection of a sublethal dose of the irreversible organophosphate sarin (0.08 mg/kg) in rats induced a non-Wallerian-type axonal degeneration of the neuromuscular synapse in the slow twitch, soleus muscle. These alterations of the endplate region were more obvious in the soleus than in the fast extensor digitorum longus muscle and were slowly reversible, complete recovery requiring about 10 days. Silver-cholinesterase staining and electrophysiological techniques were used to define the spatiotemporal evolution of prejunctional abnormalities. The non-Wallerian-type axonal degeneration of the neuromuscular synapse was characterized by bead or balloon-like varicosities of the focal, distal, and terminal nerve fibers and a retraction of terminal axons. Axonal degeneration was accompanied by junctional and extrajunctional membrane depolarization and was followed by nerve sprouting at focal, distal, and terminal nerve fibers. Transients similar to miniature endplate potentials were recorded along the muscle fiber at distances of 800-2500 microns away from the parent endplate. New ectopic endings, originating from the same endplate, were discovered adjacent to the terminal axon and also distant from the parent endplate. Very elaborate terminal arborization and occasional multibranching arose from a progressive growth sprout. The new sprouting may have served to compensate for the loss of synaptic contact caused by sarin. Thus the present study demonstrates a direct cytotoxic effect of sarin and indicates that this organophosphate agent may be an important neurotoxicological tool to understand the mechanisms involved in nerve sprouting.

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Morphological and electrophysiological study of distal motor nerve fiber degeneration and sprouting after irreversible cholinesterase inhibition

Kawabuchi

Cintra

Deshpande

et al. 1991

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Cytochemical Reevaluation of Location and Translocation of Acetylcholinesterase in the Motor End-Plate

Kreutzberg

Tóth

1987

Advances in Applied Neurological Sciences

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Morphogenesis of nuclear inclusions in the soleplate region of rat skeletal muscle fibers following chronic daily administration of neostigmine

1989

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In the course of ultrastructural investigations of motor endplate pathology mediated by calcium ions, intranuclear sarcoplasmic inclusions, either membrane-free (true type) or membrane-delimited (false type), were observed during chronic daily high-dose exposure to the anticholinesterase neostigmine. At the stage in which subjunctional components, including soleplate nuclei, were severely damaged (day 7), the true nuclear inclusions were frequently associated with the disrupted nuclear envelope (fragmentation, vesiculation etc.) and nuclear pores. At a subsequent stage, in which muscle repair was accelerated and most soleplate nuclei were less severely affected (day 21), formation of the false inclusions in these nuclei was enhanced. Analysis of serial sections of the less severely affected nuclei, where only a true inclusion type was present, revealed no sign of invaginated nuclear envelopes or other membranes enclosing the inclusions. Our findings indicate that morphogenesis of true inclusions depends upon the severity of nuclear degeneration, i.e., in severely affected nuclei there is disruption in the nuclear envelope and/or nuclear pores, while in less severely affected nuclei, either a pinched-off invagination or diffusion of excessive sarcoplasmic proteins into the nucleus via nuclear pores occurs.

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A Light and Electron Microscopic Histochemical Study on the Mechanism of Dfp‐induced Acute and Subacute Myopathy

Cited by 12 publications

References 30 publications

Morphological and electrophysiological study of distal motor nerve fiber degeneration and sprouting after irreversible cholinesterase inhibition

Morphological and electrophysiological study of distal motor nerve fiber degeneration and sprouting after irreversible cholinesterase inhibition

Cytochemical Reevaluation of Location and Translocation of Acetylcholinesterase in the Motor End-Plate

Morphogenesis of nuclear inclusions in the soleplate region of rat skeletal muscle fibers following chronic daily administration of neostigmine

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