Spatial and temporal correlation of nitric oxide synthase expression with CuZn-superoxide dismutase reduction in motor neurons following axotomy.
Axotomized neurons expressing neuronal nitric oxide synthase (nNOS) may use nitric oxide (NO), known for its antioxidant activities and ability to scavenge free radicals, to protect against oxidative stress. This hypothesis was tested by immunohistochemical examination of superoxide dismutase (SOD) in neurons of the hypoglossal nucleus (HGN) and dorsal motor nucleus of the vagus nerve (DMV) one day to ten weeks after unilateral hypoglossal nerve crush or avulsion combined with vagus nerve crush in adult rats, and also in neurons of the anterior horn (AH) one week after unilateral sciatic nerve crush or avulsion. In the HGN, emergence of nNOS coincided temporally with reduction of CuZn-SOD immunoreactivity (ir), and the level of reduction correlated with that of nNOS induction, differing only in magnitude between nerve crush and nerve avulsion. The two nerve lesion models further revealed the concurrence of nNOS abatement with recovery of CuZn-SOD ir, and absence of nNOS abatement with persistent low CuZn-SOD ir. In the AH, reduced CuZn-SOD ir was localized in the segments containing nNOS positive neurons as a result of sciatic nerve avulsion. CuZn-SOD ir was unchanged in the absence of nNOS induction following sciatic nerve crush. DMV neurons were devoid of CuZn-SOD ir. However, increased Mn-SOD ir one and two weeks post crush was similar to that in HGN neurons. DMV neurons lacked both nNOS abatement and CuZn-SOD ir, which may explain their particular vulnerability to cell death from axotomy in comparison with other peripheral neurons. These data suggest that axotomy-induced nNOS expression is causally linked to oxidative stress, and that NO is neuroprotective, but can become neurodestructive when produced in excess.
Yu
Wan-Hua Amy
WH
Department of Cell Biology and Anatomical Sciences, City University of New York Medical School, New York, New York 10031, USA. ayu@med.cuny.edu
D000818:Animals; D000870:Anterior Horn Cells / Q000166:cytology / Q000378:metabolism; D019771:Axotomy; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D061228:Hypoglossal Nerve Injuries; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D061223:Vagus Nerve Injuries
D016166:Free Radical Scavengers; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013482:Superoxide Dismutase