An electron microscopic study of endrin induced alterations in unmyelinated fibers of mouse sciatic nerve

This study examined the ultrastructural alterations in peripheral nerve of adult mouse following repeated sublethal exposures to endrin, a toxic chlorinated hydrocarbon which produces symptoms indicative of neuromuscular dysfunction. Male mice were given 20 daily ip injections of endrin in sesame oil (0.2 ml) in doses that increased from 1.5 mg/kg on days 0-3, to 2.0 mg/kg on days 4-11, and to 4.0 mg/kg on days 12-19. Controls were given the same intraperitoneal volume of sesame oil without endrin. Animals were sacrificed by glutaraldehyde perfusion after 4, 7, 14, and 20 days of exposure and 14 and 92 days postinjection and sciatic nerve tissue was prepared for electron microscopy. Myelinated nerve fibers, myelin and associated Schwann cells from endrin exposed animals appeared similar to those of controls and normal animals. Various morphological alterations were observed in many unmyelinated axons from endrin exposed animals. Such alterations included swelling, dissolution of microtubules and neurofilaments, the presence of unusual numbers of axoplasmic vesicles, both scattered and in packets, and less often, extreme vacuolation. In those Schwann cells associated with damaged axons the cytoplasm and the adaxonal space frequently contained vesicles, often in packets invaginating the axolemma. The results of this study indicate that repeated subacute doses of endrin can produce morphological alterations in unmyelinated peripheral nerve fibers and their associated Schwann cells without apparent damage to myelinated nerve fibers. The results are discussed relative to other studies producing similar nerve damage and to the potential mechanisms responsible for such damage.