Regulation of nitric oxide synthase expression in motoneurons following nerve injury

This study investigated the influence of postsynaptic targets and axonal ensheathing cells on the expression of nitric oxide synthase (NOS) in axotomized neurons. The hypoglossal and vagus nerves of adult rats were lesioned unilaterally, and axotomized neurons expressing NOS, identified by NADPH-diaphorase histochemistry and NOS immunocytochemistry, were counted as a function of time between 1 and 70 days postaxotomy. In the dorsal motor nucleus of the vagus (DMV), the number of NOS-positive neurons increased steadily with a time course which was not significantly different between the nerve crushed and transected groups. In the hypoglossal nucleus, each of four axotomy groups, namely, crushed, transected, ligated/transected, and avulsed, exhibited a distinct time course and extent of NOS expression, suggesting that postsynaptic targets and axonal ensheathing cells regulated NOS expression. The disparity between hypoglossal and DMV neurons in NOS expression may be due to the latters' unresponsiveness to, or inability to obtain the proper regulatory signals. Since cell loss was most severe in the hypoglossal nucleus following nerve avulsion, it appears that prolonged expression of NOS at high levels may be neurotoxic.