ArticleSleep2016
Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice.
Article in Sleep, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Review
- Bidirectional sleep-seizure interactions and orexin in a mouse model of tuberous sclerosis complex-related epilepsy.Epilepsia · 2026Article
- Exploring Linalool-Based Phytotherapy for Excitatory/Inhibitory Imbalance in Alzheimer's Disease: A Review of Lavender and Cannabis Therapeutic Effects on Sleep, Seizures, and Cognition.Phytotherapy research : PTR · 2026Review
- Article
- Targeted Reduction of Excessive Mitochondrial Superoxide by Mitoquinone Rescues Cognitive Impairment Without Affecting Spontaneous Recurrent Seizures in a Mouse Model of Temporal Lobe Epilepsy.Antioxidants (Basel, Switzerland) · 2026Article
- Allostatic load of immune cells in the spleen and brain of the Kcna1-null mouse model of temporal lobe epilepsy.Epilepsy research · 2026Article
- 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
- Development and characterization of an autoresuscitation test for preclinical SUDEP models.Epilepsia · 2025Article
- Advances and challenges in experimental models of posttraumatic epilepsy for therapeutic interventions.Pharmacological reviews · 2025Review
- Review
- Article
- Sudden Unexpected Death in Epilepsy: A Narrative Review of Mechanism, Risks, and Prevention.Journal of clinical medicine · 2025Review
- Mechanistic insights into the interaction between epilepsy and sleep.Nature reviews. Neurology · 2025Review
- Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.International journal of molecular sciences · 2025Review
- Article
- Influence of sleep on seizures and interictal epileptiform discharges in epilepsy.Encephalitis (Seoul, Korea) · 2025Article
- Metabolic aspects of genetic ion channel epilepsies.Journal of neurochemistry · 2024Review
- Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons.Neurobiology of disease · 2024Article
- Review
- Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy.Nature communications · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
STUDY
objectiveComorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy.
methodsRest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography.
resultsKcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice.
conclusionDual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models.
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