Neostigmine-induced alterations at the mammalian neuromuscular junction. II. Ultrastructure

Area of Science:

• Neurology
• Muscle Physiology
• Pharmacology

Background:

• Neostigmine methylsulfate is commonly used for myasthenia gravis.
• Its long-term effects on neuromuscular junctions require detailed investigation.

Purpose of the Study:

• To investigate the morphological effects of neostigmine methylsulfate on rat muscle end-plates.
• To determine if observed changes result from direct drug interaction or increased synaptic activity.

Main Methods:

• Rats were exposed to neostigmine methylsulfate for brief and chronic periods.
• Morphological analysis of the extensor digitorum longus muscle end-plate region was performed using electron microscopy.
• Effects were compared between treated, denervated, and chronically denervated muscle fibers.

Main Results:

• Neostigmine induced dose- and time-dependent morphological alterations at the neuromuscular junction.
• Presynaptic changes included synaptic vesicle depletion and increased coated vesicles, indicating nerve terminal hyperactivity.
• Postsynaptic changes were primarily observed in nondenervated fibers and were absent after denervation, suggesting activity-dependent damage.

Conclusions:

• Neostigmine-induced myopathic changes result from heightened synaptic activity, not direct membrane effects.
• Long-term neostigmine therapy outside of crisis situations may carry risks due to these morphological changes.