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

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.