Melatonin attenuates the neuronal NADPH-d/NOS expression in the nodose ganglion of acute hypoxic rats.
Excessive production of nitric oxide (NO) may play a detrimental role in the process of hypoxia-related neuropathology. This study explored whether treatment with melatonin would attenuate the neuropathological changes in the vagal ganglia following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment, young adult rats were pre-treated with melatonin at 5. 25 or 100 mg/kg injected intraperitoneally. Hypoxia was achieved by subjecting the rats to a barometric pressure of 0.2 atm (PO2 = 43 Torr) for 4 hr in an altitude chamber. Nicotinamine adenine dinucleotide phosphatediaphorase (NADPH-d) histochemistry combined with the neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to detect the NADPH-d/nNOS reactivity in the nodose ganglion (NG) at various time points following the hypoxic exposure. In normal untreated rats, about 43% of the neurons in the NG displayed NADPH-d/nNOS reactivity. Following hypoxic exposure, both the percentage and the staining intensity of NADPH-d/nNOS positive neurons in the NG were markedly increased, but these were reduced in longer surviving animals. Quantitative analysis of cell counts revealed that about 17% of the neurons died at 14 days after hypoxia treatment. However, in hypoxic rats given different doses of melatonin pretreatment, neuronal death as well as the frequency and staining intensity of NADPH-d/nNOS reactivity of the nodose neurons were significantly decreased. The effect of melatonin on neuronal survival and NADPH-d/ nNOS expression was dose-dependent. It is therefore suggested that melatonin exerts a neuroprotective effect and may serve as a potential therapeutic strategy for prevention and/or reducing the susceptibility of nodose neurons to NO-mediated hypoxic neuropathy.
Chang
Hung-Ming
HM
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei.
Ling
Eng-Ang
EA
Chen
Chau-Fong
CF
Lue
Horng
H
Wen
Chen-Yuan
CY
Shieh
Jeng-Yung
JY
D000818:Animals; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D009252:NADPH Dehydrogenase; D008550:Melatonin