ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Nitric oxide mediates selective degeneration of hypothalamic orexin neurons through dysfunction of protein disulfide isomerase.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.Journal of advanced research · 2026Review
- Kainic acid status epilepticus - induced changes in the hippocampus and hypothalamus alter the effects of exogenous Orexin-A in the hippocampus.IBRO neuroscience reports · 2025Article
- Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia.Nature. Mental health · 2024Article
- Infections, Pandemics, and Sleep Disorders.Neuroscience and behavioral physiology · 2022Article
- The Role of Protein S-Nitrosylation in Protein Misfolding-Associated Diseases.Life (Basel, Switzerland) · 2021Review
- PDI-Regulated Disulfide Bond Formation in Protein Folding and Biomolecular Assembly.Molecules (Basel, Switzerland) · 2020Review
- Energy Metabolism Decline in the Aging Brain-Pathogenesis of Neurodegenerative Disorders.Metabolites · 2020Review
- PDI-mediated S-nitrosylation of DRP1 facilitates DRP1-S616 phosphorylation and mitochondrial fission in CA1 neurons.Cell death & disease · 2018Article
- Neural Damage in ExperimentalFrontiers in neuroanatomy · 2018Article
- Mild endoplasmic reticulum stress ameliorates lipopolysaccharide-induced neuroinflammation and cognitive impairment via regulation of microglial polarization.Journal of neuroinflammation · 2017Article
- Promotion of the Unfolding Protein Response in Orexin/Dynorphin Neurons in Sudden Infant Death Syndrome (SIDS): Elevated pPERK and ATF4 Expression.Molecular neurobiology · 2017Article
- Article
- Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage.Frontiers in cellular neuroscience · 2017Article
- Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.PLoS neglected tropical diseases · 2016Article
- Article
- Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons.Molecular endocrinology (Baltimore, Md.) · 2016Article
- H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Aberrant protein S-nitrosylation contributes to the pathophysiology of neurodegenerative diseases.Neurobiology of disease · 2015Review
- Sleep disruption and the sequelae associated with traumatic brain injury.Neuroscience and biobehavioral reviews · 2015Review
- Interactions of the histamine and hypocretin systems in CNS disorders.Nature reviews. Neurology · 2015Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We addressed the role of nitric oxide (NO) in orexin neuron degeneration that has been observed under various pathological conditions. Administration of an NO donor NOC18 (50 nmol) into the third ventricle of mice resulted in a significant decrease of orexin-immunoreactive (-IR) neurons, in contrast to a modest change in melanin-concentrating hormone-IR neurons. In addition, NOC18 promoted formation of orexin-A-IR aggregates within orexin neurons. An endoplasmic reticulum stress inducer tunicamycin replicated the effect of NOC18 with regard to decrease of orexin-IR neurons and formation of aggregates. We also found that NOC18 caused an increase in S-nitrosation of protein disulfide isomerase (PDI) and a decrease in PDI activity in hypothalamic tissues. Moreover, PDI inhibitors, such as cystamine and securinine, caused a selective decrease of orexin neurons and promoted formation of orexin-A-IR aggregates. Aggregate formation in orexin-IR neurons was also induced by local injection of small interfering RNA targeting PDI. Interestingly, sleep deprivation for 7 consecutive days induced a selective decrease of orexin-IR neurons, which was preceded by aggregate formation in orexin-IR neurons and an increase in S-nitrosated PDI in the hypothalamus. Activity of neuronal NO synthase (nNOS)-positive neurons in the lateral hypothalamus as assessed by c-Fos expression was elevated in response to sleep deprivation. Finally, sleep deprivation-induced decrease of orexin-IR neurons, formation of aggregates, and S-nitrosation of PDI were not observed in nNOS knock-out mice. These results indicate that nNOS-derived NO may mediate specific pathological events in orexin neurons, including neuropeptide misfolding via S-nitrosation and inactivation of PDI.
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