Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury.
Peripheral nerve injury (PNI) produces functional changes in lesioned neurons in which oxidative stress is considered to be the main cause of neuronal damage. As superoxide dismutase (SOD) is an important antioxidative enzyme involved in redox regulation of oxidative stress, the present study determined whether melatonin would exert its beneficial effects by preserving the SOD reactivity following PNI. Adult rats subjected to hypoglossal nerve transection were intraperitoneally injected with melatonin at ones for 3, 7, 14, 30 and 60 days successively. The potential neuroprotective effects of melatonin were quantitatively demonstrated by neuronal nitric oxide synthase (nNOS), mitochondrial manganese SOD (Mn-SOD), and cytosolic copper-zinc SOD (Cu/Zn-SOD) immunohistochemistry. The functional recovery of the lesioned neurons was evaluated by choline acetyltransferase (ChAT) immunohistochemistry along with the electromyographic (EMG) recordings of denervation-induced fibrillation activity. The results indicate that following PNI, the nNOS immunoreactivity was significantly increased in lesioned neurons peaking at 14 days. The up-regulation of nNOS temporally coincided with the reduction of ChAT and SOD in which the Cu/Zn-SOD showed a greater diminution than Mn-SOD. However, following melatonin administration, the nNOS augmentation was successfully suppressed and the activities of Mn-SOD, Cu/Zn-SOD, and ChAT were effectively preserved at all postaxotomy periods. EMG data also showed a decreased fibrillation in melatonin-treated groups, suggesting a potential effect of melatonin in promoting functional recovery. In association with its significant capacity in preserving SOD reactivity, melatonin is suggested to serve as a powerful therapeutic agent for treating PNI-relevant oxidative damage.
Chang
Hung-Ming
HM
Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung, Taiwan. anatomy@csmu.edu.tw
Huang
Yi-Lun
YL
Lan
Chyn-Tair
CT
Wu
Un-In
UI
Hu
Ming-E
ME
Youn
Su-Chung
SC
D000818:Animals; D004576:Electromyography; D004789:Enzyme Activation / Q000187:drug effects; D007002:Hypoglossal Nerve / Q000201:enzymology / Q000378:metabolism*; D061228:Hypoglossal Nerve Injuries; D008297:Male; D008550:Melatonin / Q000502:physiology*; D009046:Motor Neurons / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*
D013482:Superoxide Dismutase; D008550:Melatonin