{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:47:51Z","timestamp":1782197271357,"version":"3.54.5"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Narcolepsy is a rare sleep disorder characterized by cataplexy and excessive daytime sleepiness. The hallmark neuropathological feature is the selective loss of hypothalamic hypocretin (HCRT) neurons. This review systematically summarizes the roles of neuroimmune dysregulation, HCRT neuron loss, and neural circuit remodeling in the pathogenesis of narcolepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Web of Science, and Scopus from 1990 through April 2026. Search terms included narcolepsy, hypocretin\/orexin, autoimmunity, HLA, T cell, neural circuit, brain network, and functional connectivity. Articles were included if they were in English, peer-reviewed, and provided mechanistic insights. In addition, key references identified in the search articles were included.We organized the review according to a conceptual framework linking immune dysregulation, hypocretin neuron loss, sleep\u2013wake circuit imbalance, and large-scale brain network reconfiguration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetic susceptibility and environmental triggers collectively promote an immune-mediated attack, causing irreversible loss of lateral hypothalamic HCRT neurons. This disruption impairs sleep-wake circuit homeostasis and upsets the balance between REM-off and REM-on neurons. Consequently, brain network remodeling and functional instability ensue, manifesting as excessive daytime sleepiness, cataplexy, and cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This review provides a theoretical framework integrating immunity, neural circuitry, and brain network reconfiguration in narcolepsy pathophysiology. Understanding these mechanisms may identify potential diagnostic biomarkers and therapeutic targets for narcolepsy, particularly for type 1 narcolepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1864667","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:11:56Z","timestamp":1782195116000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Narcolepsy: immunity, neural circuitry, and brain network reconfiguration"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiajia","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Sleep Medicine, Guizhou Provincial Second People\u2019s Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine, Guizhou Provincial Second People\u2019s Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jinyang Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youde","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jinyang Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Graduate School, Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14277","article-title":"Narcolepsy and rapid eye movement sleep","volume":"34","author":"Biscarini","year":"2025","journal-title":"J Sleep Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.9328","article-title":"Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline","volume":"17","author":"Maski","year":"2021","journal-title":"J Clin Sleep Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2021.03.014","article-title":"2018 worldwide survey of health-care providers caring for patients with narcolepsy: WSS narcolepsy task force","volume":"82","author":"Rosenthal","year":"2021","journal-title":"Sleep Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1159\/000525282","article-title":"Heterogeneity in estimates of incidence and prevalence of narcolepsy: a systematic review and meta-regression analysis","volume":"56","author":"Wang","year":"2022","journal-title":"Neuroepidemiology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.70984","article-title":"Orexin deficiency in narcolepsy: molecular mechanisms, clinical phenotypes, and emerging therapeutic frontiers","volume":"15","author":"Rauf","year":"2025","journal-title":"Brain Behav"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1379723","article-title":"Correlation analysis between HLA-DQA1*0102\/DQB1*0602 genotypes and narcolepsy patients in China","volume":"15","author":"Zhao","year":"2024","journal-title":"Front Neurol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.11300","article-title":"Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study","volume":"20","author":"Bacelar","year":"2024","journal-title":"J Clin Sleep Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1835903","article-title":"The impact of the HLA DQB1 gene and amino acids on the development of narcolepsy","volume":"132","author":"Kachooei-Mohaghegh-Yaghoobi","year":"2022","journal-title":"Int J Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2513989122","article-title":"HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity","volume":"122","author":"Zhang","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1055\/s-0044-1779299","article-title":"Narcolepsy: an interface among neurology, immunology, sleep, and genetics","volume":"82","author":"Coelho","year":"2024","journal-title":"Arq Neuropsiquiatr"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S275931","article-title":"Reviewing the clinical implications of treating narcolepsy as an autoimmune disorder","volume":"13","author":"Giannoccaro","year":"2021","journal-title":"Nat Sci Sleep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-020-0609-7","article-title":"Immunotherapy in narcolepsy","volume":"22","author":"Giannoccaro","year":"2020","journal-title":"Curr Treat Options Neurol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.280322","article-title":"Differences in clinical and genetic characteristics between early- and late-onset narcolepsy in a Han Chinese cohort","volume":"15","author":"Ouyang","year":"2020","journal-title":"Neural Regener Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsab062","article-title":"High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1","volume":"44","author":"Viste","year":"2021","journal-title":"Sleep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-020-01784-5","article-title":"Cerebellar ataxia as a common clinical presentation associated with DNMT1 p.Y511H and a review of the literature","volume":"71","author":"Kikuchi","year":"2021","journal-title":"J Mol Neurosci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000456","article-title":"Expanded genetic insight and clinical experience of DNMT1-complex disorder","volume":"6","author":"Bi","year":"2020","journal-title":"Neurol Genet"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521463112","article-title":"H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice","volume":"113","author":"Tesoriero","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13631","article-title":"Narcolepsy","volume":"31","author":"Barateau","year":"2022","journal-title":"J Sleep Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.47936\/encephalitis.2021.00010","article-title":"Narcolepsy, autoimmunity, and influenza A H1N1 vaccination","volume":"1","author":"Sunwoo","year":"2021","journal-title":"ncephalitis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsae014","article-title":"Downregulation of hypocretin\/orexin after H1N1 Pandemrix vaccination of adolescent mice","volume":"47","author":"Pagh-Berendtsen","year":"2024","journal-title":"Sleep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2019.03.017","article-title":"The olfactory bulb: a link between environmental agents and narcolepsy","volume":"126","author":"Mori","year":"2019","journal-title":"Med Hypotheses"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsad005","article-title":"What triggered narcolepsy: H1N1 vaccination, virus, or both? Important lessons learned from China","volume":"46","author":"Gool","year":"2023","journal-title":"Sleep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2024.02.033","article-title":"Potential immunological triggers for narcolepsy and idiopathic hypersomnia: real-world insights on infections and influenza vaccinations","volume":"116","author":"Gool","year":"2024","journal-title":"Sleep Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205797119","article-title":"Characterization of T cell receptors reactive to HCRTNH2, pHA273-287, and NP17-31 in control and narcolepsy patients","volume":"119","author":"Luo","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2022.10.004","article-title":"Repeated measures of hypocretin-1 in Danish and Italian patients with narcolepsy and in controls","volume":"101","author":"Torstensen","year":"2023","journal-title":"Sleep Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ana.78199","article-title":"Increased numbers of CD4+ T-cells in the hypocretin\/orexin region of narcolepsy type 1","volume":"99","author":"Shan","year":"2026","journal-title":"Ann Neurol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/bs.ai.2022.10.001","article-title":"T cells in the brain inflammation","volume":"157","author":"Yoshimura","year":"2023","journal-title":"Adv Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1038\/s41467-023-36120-z","article-title":"Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy","volume":"14","author":"Ollila","year":"2023","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1186\/s12883-025-04359-2","article-title":"Association between cytokines and neuropsychiatric symptoms in paediatric narcolepsy patients: a cross-sectional study","volume":"25","author":"Wei","year":"2025","journal-title":"BMC Neurol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2023.12.005","article-title":"Connecting the dots: an updated review of the role of autoimmunity in narcolepsy and emerging immunotherapeutic approaches","volume":"113","author":"Valizadeh","year":"2024","journal-title":"Sleep Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1249405","article-title":"The transcriptomics profiling of blood CD4 and CD8 T-cells in narcolepsy type I","volume":"14","author":"Khajavi","year":"2023","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41577-023-00902-9","article-title":"The immunopathogenesis of narcolepsy type 1","volume":"24","author":"Liblau","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab455","article-title":"Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy","volume":"145","author":"Bernard-Valnet","year":"2022","journal-title":"Brain"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.11056","article-title":"Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy","volume":"20","author":"Zhong","year":"2024","journal-title":"J Clin Sleep Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jaut.2013.06.010","article-title":"Passive transfer of narcolepsy: anti-TRIB2 autoantibody positive patient IgG causes hypothalamic orexin neuron loss and sleep attacks in mice","volume":"45","author":"Katzav","year":"2013","journal-title":"J Autoimmun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2024.578383","article-title":"Infection, vaccination and narcolepsy type 1: evidence and potential molecular mechanisms","volume":"393","author":"Ayoub","year":"2024","journal-title":"J Neuroimmunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12688","article-title":"High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2","volume":"51","author":"Hamdan","year":"2024","journal-title":"Int J Immunogenet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2019.1643843","article-title":"Autoantibodies in Pandemrix\u00ae-induced narcolepsy: nine candidate autoantigens fail the conformational autoantibody test","volume":"52","author":"Wallenius","year":"2019","journal-title":"Autoimmunity"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.902840","article-title":"Narcolepsy and H1N1 influenza immunology a decade later: what have we learned","volume":"13","author":"Buonocore","year":"2022","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2024.02.031","article-title":"Cortical thickness and sub-cortical volumes in post-H1N1 narcolepsy type 1: a brain-wide MRI case-control study","volume":"116","author":"Juvodden","year":"2024","journal-title":"Sleep Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0388-9","article-title":"Physiology of gangliosides and the role of antiganglioside antibodies in human diseases","volume":"17","author":"Cutillo","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0297625","article-title":"Absence of specific autoantibodies in patients with narcolepsy type 1 as indicated by an unbiased random peptide-displayed phage screening","volume":"19","author":"Tran","year":"2024","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2021.07.024","article-title":"Narcolepsy type 1 patients have lower levels of effector memory CD4+ T cells compared to their siblings when controlling for H1N1-(Pandemrix\u2122)-vaccination and HLA DQB1\u221706:02 status","volume":"85","author":"Viste","year":"2021","journal-title":"Sleep Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12864","article-title":"Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays","volume":"91","author":"Lind","year":"2020","journal-title":"Scand J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"997","DOI":"10.3881\/j.issn.1000-503X.16463","article-title":"Research progress in the roles of influenza A H1N1 virus and its vaccine in the pathogenesis of narcolepsy type 1","volume":"47","author":"Ding","year":"2025","journal-title":"Acta Academiae Medicinae Sinicae"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171009","article-title":"Internal and external modulation factors of the orexin system (review)","volume":"165","author":"Maruyama","year":"2023","journal-title":"Peptides"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsad173","article-title":"Larger hypothalamic volume in narcolepsy type 1","volume":"46","author":"Juvodden","year":"2023","journal-title":"Sleep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaf237","article-title":"16-mer hypocretin-1\/orexin-A in cerebrospinal fluid to diagnose narcolepsy","volume":"48","author":"Vialaret","year":"2025","journal-title":"Sleep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/26.3.287","article-title":"Decreased hypocretin-1 (orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness","volume":"26","author":"Mart\u00ednez-Rodr\u00edguez","year":"2003","journal-title":"Sleep"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2024.149408","article-title":"The mechanism of different orexin\/hypocretin neuronal projections in wakefulness and sleep","volume":"1850","author":"Li","year":"2025","journal-title":"Brain Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0167-0115(99)00076-2","article-title":"Orexins and orexin receptors: implication in feeding behavior","volume":"85","author":"Sakurai","year":"1999","journal-title":"Regul Pept"},{"key":"B52","doi-asserted-by":"publisher","first-page":"5979","DOI":"10.1038\/s41467-024-50166-7","article-title":"Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture","volume":"15","author":"Braga","year":"2024","journal-title":"Nat Commun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171007","article-title":"The role of orexin neuron activity in sleep\/wakefulness regulation","volume":"165","author":"Hung","year":"2023","journal-title":"Peptides"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000147328.15956.b4","article-title":"CSF hypocretin-1 (orexin-A) levels in childhood narcolepsy and neurologic disorders","volume":"63","author":"Arii","year":"2004","journal-title":"Neurology"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1230428","article-title":"Orexin and MCH neurons: regulators of sleep and metabolism","volume":"17","author":"Bou\u00e2ouda","year":"2023","journal-title":"Front Neurosci"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1590556","article-title":"The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance","volume":"19","author":"Li","year":"2025","journal-title":"Front Neurosci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301951120","article-title":"Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy","volume":"120","author":"Ito","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"B58","doi-asserted-by":"publisher","first-page":"4163","DOI":"10.1038\/s41467-022-31591-y","article-title":"Orexin neurons inhibit sleep to promote arousal","volume":"13","author":"De Luca","year":"2022","journal-title":"Nat Commun"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47110874","article-title":"Animal models of narcolepsy: from orexin deficiency to immune mechanisms and regenerative therapies","volume":"47","author":"Arias-Carri\u00f3n","year":"2025","journal-title":"Curr Issues Mol Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.11477\/mf.188160960770101053","article-title":"Neural circuit mechanisms underlying REM sleep","volume":"77","author":"Watanabe","year":"2025","journal-title":"Brain Nerve"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115277","article-title":"Orexin\/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity","volume":"44","author":"Izawa","year":"2025","journal-title":"Cell Rep"},{"key":"B62","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1016\/j.cub.2025.03.040","article-title":"An orexin agonist promotes wakefulness and inhibits cataplexy through distinct brain regions","volume":"35","author":"Ishikawa","year":"2025","journal-title":"Curr Biol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41398-025-03684-x","article-title":"Attention and inhibition deficits in narcolepsy type 1: behavioral and electrophysiological markers","volume":"15","author":"Li","year":"2025","journal-title":"Transl Psychiatry"},{"key":"B64","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.neubiorev.2015.03.009","article-title":"Gray matter atrophy in narcolepsy: an activation likelihood estimation meta-analysis","volume":"59","author":"Weng","year":"2015","journal-title":"Neurosci Biobehav Rev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbscr.2025.100137","article-title":"Neuroimaging findings in sleep disorders: a review article","volume":"20","author":"Kavehee","year":"2025","journal-title":"Neurobiol Sleep Circadian Rhythms"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2025.02.020","article-title":"White matter changes in patients with narcolepsy type 2: peak width of skeletonized mean diffusivity study","volume":"129","author":"Kang","year":"2025","journal-title":"Sleep Med"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.70209","article-title":"Dynamic functional network connectivity patterns distinguish neurobiological substrates of narcolepsy type 1 and idiopathic hypersomnia: potential biomarkers from resting-state fMRI","volume":"35","author":"Mengmeng","year":"2026","journal-title":"J Sleep Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-025-08009-w","article-title":"Pons metabolite alterations in narcolepsy type 1","volume":"46","author":"Mitolo","year":"2025","journal-title":"Neurol Sci"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-015-9450-0","article-title":"Morphological alterations in amygdalo-hippocampal substructures in narcolepsy patients with cataplexy","volume":"10","author":"Kim","year":"2016","journal-title":"Brain Imaging Behav"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12785","article-title":"Anterior hippocampus volume loss in narcolepsy with cataplexy","volume":"28","author":"K\u0159e\u010dkov\u00e1","year":"2019","journal-title":"J Sleep Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70130","article-title":"Sleep disorders: pathogenesis and therapeutic interventions","volume":"6","author":"Liu","year":"2025","journal-title":"MedComm (2020)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16195","article-title":"Orexin increases the neuronal excitability of several brain areas associated with maintaining of arousal","volume":"168","author":"Chen","year":"2024","journal-title":"J Neurochem"},{"key":"B73","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.1016\/j.cub.2021.06.031","article-title":"The NAergic locus coeruleus-ventrolateral preoptic area neural circuit mediates rapid arousal from sleep","volume":"31","author":"Liang","year":"2021","journal-title":"Curr Biol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-025-06839-2","article-title":"The orexin\/hypocretin system in dementia-related neurological disorders: a double-edged sword in cognitive impairment","volume":"242","author":"Zhuang","year":"2025","journal-title":"Psychopharmacol (Berl)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2025.10.008","article-title":"Cracking the complexity of REM sleep","volume":"48","author":"Dong","year":"2025","journal-title":"Trends Neurosci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/nature04767","article-title":"A putative flip-flop switch for control of REM sleep","volume":"441","author":"Lu","year":"2006","journal-title":"Nature"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0291-25.2025","article-title":"Sleep-wake states are encoded across emotion regulation regions of the mouse brain","volume":"12","author":"Walder-Christensen","year":"2025","journal-title":"eNeuro"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107613","article-title":"Dopamine release in the nucleus accumbens promotes REM sleep and cataplexy","volume":"26","author":"Toth","year":"2023","journal-title":"iScience"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70141","article-title":"Dorsal raphe serotonergic neurons-ventral tegmental area neural pathway promotes wake from sleep","volume":"30","author":"Wang","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"B80","doi-asserted-by":"publisher","first-page":"3922","DOI":"10.1038\/s41467-023-39496-0","article-title":"A medullary hub for controlling REM sleep and pontine waves","volume":"14","author":"Schott","year":"2023","journal-title":"Nat Commun"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.34133\/research.0355","article-title":"Orexin neurons to sublaterodorsal tegmental nucleus pathway prevents sleep onset REM sleep-like behavior by relieving the REM sleep pressure","volume":"7","author":"Feng","year":"2024","journal-title":"Res (Wash D C)"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.97","article-title":"Cataplexy--clinical aspects, pathophysiology and management strategy","volume":"10","author":"Dauvilliers","year":"2014","journal-title":"Nat Rev Neurol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1749306","article-title":"Differential motor signatures in isolated and narcolepsy-related REM sleep behaviour disorder: a preliminary study","volume":"16","author":"Drakatos","year":"2026","journal-title":"Front Neurol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2025.103751","article-title":"Lesion network mapping of REM sleep behaviour disorder","volume":"45","author":"Odd","year":"2025","journal-title":"NeuroImage Clin"},{"key":"B85","doi-asserted-by":"publisher","first-page":"8668","DOI":"10.1038\/s41598-026-42639-0","article-title":"Mapping nocturnal arousal across sleep and pain disorders","volume":"16","author":"Biabani","year":"2026","journal-title":"Sci Rep"},{"key":"B86","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/s41398-025-03670-3","article-title":"Hypothalamic functional connectivity, depressive symptoms, and post-treatment SOREMPs in narcolepsy type 1: links to sleep latency and mediation mechanisms","volume":"15","author":"Wang","year":"2025","journal-title":"Transl Psychiatry"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1152594","article-title":"Amygdala neurocircuitry at the interface between emotional regulation and narcolepsy with cataplexy","volume":"17","author":"Sardar","year":"2023","journal-title":"Front Neurosci"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1016\/j.cub.2025.02.053","article-title":"Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice","volume":"35","author":"Guillaumin","year":"2025","journal-title":"Curr Biol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1016\/j.neuron.2023.07.007","article-title":"A common thalamic hub for general and defensive arousal control","volume":"111","author":"Wang","year":"2023","journal-title":"Neuron"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2025.101962","article-title":"Unraveling the pathophysiology of narcolepsy type 1 through hypothesis-driven and hypothesis-generating approaches","volume":"78","author":"Freeman","year":"2025","journal-title":"Semin Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0706-12.2012","article-title":"Optogenetic probing of fast glutamatergic transmission from hypocretin\/orexin to histamine neurons in situ","volume":"32","author":"Sch\u00f6ne","year":"2012","journal-title":"J Neurosci"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-23-09273.2001","article-title":"Orexin\/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus","volume":"21","author":"Eriksson","year":"2001","journal-title":"J Neurosci"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2220911120","article-title":"Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy","volume":"120","author":"Seifinejad","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102748","article-title":"Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1","volume":"31","author":"Ballotta","year":"2021","journal-title":"NeuroImage Clin"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.904820","article-title":"Enhanced visual cortex activation in people with narcolepsy type 1 during active sleep resistance: an fMRI-EEG study","volume":"16","author":"Gool","year":"2022","journal-title":"Front Neurosci"},{"key":"B96","doi-asserted-by":"publisher","first-page":"3630","DOI":"10.1038\/s41598-025-33669-1","article-title":"Disorder-specific alterations of transient oscillatory dynamics during sleep across cortical and subcortical networks","volume":"16","author":"Biabani","year":"2026","journal-title":"Sci Rep"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.11566","article-title":"Current knowledge on the pathophysiology of idiopathic hypersomnia and potential mechanisms of action for low-sodium oxybate treatment","volume":"21","author":"Schneider","year":"2025","journal-title":"J Clin Sleep Med"},{"key":"B98","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41593-022-01236-w","article-title":"Neuro-orchestration of sleep and wakefulness","volume":"26","author":"Sulaman","year":"2023","journal-title":"Nat Neurosci"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2024.101976","article-title":"REM sleep in narcolepsy","volume":"77","author":"Thorpy","year":"2024","journal-title":"Sleep Med Rev"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26736","article-title":"Activated wake systems in narcolepsy type 1","volume":"94","author":"Shan","year":"2023","journal-title":"Ann Neurol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171080","article-title":"The role of orexinergic system in the regulation of cataplexy","volume":"169","author":"Koyama","year":"2023","journal-title":"Peptides"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhad532","article-title":"Predictable and unpredictable deviance detection in the human hippocampus and amygdala","volume":"34","author":"Tzovara","year":"2024","journal-title":"Cereb Cortex"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.sleep.2024.04.004","article-title":"MRS study on the correlation between frontal GABA+\/Glx ratio and abnormal cognitive function in medication-naive patients with narcolepsy","volume":"119","author":"Gao","year":"2024","journal-title":"Sleep Med"},{"key":"B104","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.pediatrneurol.2024.01.015","article-title":"Microstructural white matter abnormalities in children and adolescents with narcolepsy type 1","volume":"153","author":"Hovi","year":"2024","journal-title":"Pediatr Neurol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.acra.2023.08.026","article-title":"Resting-state functional magnetic resonance imaging as an indicator of neuropsychological changes in type 1 narcolepsy","volume":"31","author":"Xu","year":"2024","journal-title":"Acad Radiol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2024.103697","article-title":"The brain topological alterations in the structural connectome and correlations with clinical characteristics in type 1 narcolepsy","volume":"44","author":"Zhang","year":"2024","journal-title":"NeuroImage Clin"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsae020","article-title":"White matter integrity in narcolepsy: the structural blueprint for functional complaints","volume":"47","author":"Gool","year":"2024","journal-title":"Sleep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864667\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:11:58Z","timestamp":1782195118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864667\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":107,"alternative-id":["10.3389\/fimmu.2026.1864667"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1864667","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"article-number":"1864667"}}