Nitric oxide synthase in motor neurons after axotomy

Abstract

Nitric oxide synthase (NOS), an enzyme involved in synthesis of nitric oxide (NO), has been localized in many diverse cell types. In the CNS and PNS, discrete neuron cell groups express NOS constitutively. Recent evidence indicates that NOS is inducible in neurons normally not expressing NOS. After transection of peripheral nerves, NOS expression was significantly up-regulated in the axotomized sensory ganglion cells, whereas in the corresponding motor neurons NOS was not induced unless axon regeneration was prevented and ensuing neuron death became massive. Studies on axotomy-induced NOS have been limited largely to spinal nerves, with only one reported in the vagus nerve. The aim of this study was to determine whether NOS induction in motor neurons of the brainstem after axotomy is regulated in a manner similar to that of the spinal cord. By NADPH-diaphorase histochemistry and NOS immunocytochemistry, the status of NOS in neurons of the hypoglossal nucleus, dorsal motor nucleus of the vagus, and motor nucleus of the facial nerve was examined 2 weeks after unilateral transection of the respective cranial nerves, and the results were compared with those of spinal motor neurons after transection of the sciatic nerve. NOS, undetectable in neurons of the three cranial motor nuclei of sham-operated animals, was observed in about 30-50% of neurons in the cranial motor nuclei ipsilateral to axotomy, but it was not detected in spinal motor neurons after axotomy. NOS localized in axotomized cranial motor neurons was unrelated to NOS of macrophages or endothelial cells. There was no appreciable cell loss from axotomy at this period except in the dorsal motor nucleus of the vagus, where some loss was observed. The results indicate that there is a fundamental difference in the regulation of NOS expression between motor neurons of the cranial and spinal nerves. The possible role of NOS/NO acting as cytoprotective or cytotoxic agent on injured motor neurons is discussed. Motor neurons of cranial and spinal nerves may serve as a useful model to further define the roles of NOS/NO in neurons, especially after traumatic injury.