Melatonin attenuates the neuronal NADPH-d/NOS expression in the nodose ganglion of acute hypoxic rats

Hung Ming Chang, Eng Ang Ling, Chau Fong Chen, June Horng Lue, Chen Yuan Wen, Jeng Yung Shieh

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35 Citations (Scopus)


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 phosphate-diaphorase (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.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalJournal of Pineal Research
Issue number2
Publication statusPublished - 2002


  • Histochemistry
  • Hypoxia
  • Immunohistochemistry
  • Melatonin
  • Nitric oxide synthase
  • Nodose ganglion

ASJC Scopus subject areas

  • Endocrinology


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