Ultrastructural analysis of mouse levator auris longus muscle intoxicated in vivo by botulinum neurotoxin type A

We studied the short and long term ultrastructural changes produced by botulinum neurotoxin type A injected in vivo, at a sublethal dose, in mouse levator auris longus muscle. The neurotoxin had a temporary effect on nerve terminals which consisted in a generalized paralysis, that affected the following features of the neuromuscular sample's morphology: size of the nerve terminals, vesicle population, mitochondrial appearance, Schwann cell's morphology, development and distribution of post-synaptic membrane folds, and nuclear morphology of the different elements of the motor end plate. Besides, the amount of endomysial connective tissue was significantly greater compared to non-intoxicated cases, and these changes were more notorious during the first couple of weeks. 20 to 25 days after the injection, during the recovery phase, we observed nerve terminals with a variable appearance: some completely degenerated, enveloped by Schwann cell processes, and new contacts characterized ultrastructurally for their small size, scarce vesicles, partially enveloped by Schwann cells, early myelinized axons and barely developed synaptic folds. Sixty days after the injection, the axon terminal recovered its normal appearance: synaptic vesicles filled the axon's cytoplasm, and the mitochondria showed normal appearing cristae and electronic densities. We conclude that botulinum neurotoxin type A produces changes related to denervation of the nerve terminals and affects the motor end plate components. Schwann cells play an important role both in the morphofuntional recovery of nerve terminals and in their degradation