{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:44:55Z","timestamp":1791935095475,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K09830"],"award-info":[{"award-number":["25K09830"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K08342"],"award-info":[{"award-number":["23K08342"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K18709"],"award-info":[{"award-number":["25K18709"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005927","name":"Daiichi Sankyo Foundation of Life Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005927","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007591","name":"Akiyama Life Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007591","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007697","name":"Northern Advancement Center for Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007697","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. In addition to motor symptoms, excessive daytime sleepiness (EDS) occurs frequently in patients with PD and severely impairs their quality of life. Current pharmacotherapies for EDS in PD are often associated with adverse effects. However, clinical studies have yielded inconsistent results, underscoring the need for safer, more effective treatment strategies. Histamine plays a pivotal role in maintaining wakefulness in the brain and is primarily inactivated by histamine\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyltransferase (HNMT), the major enzyme responsible for histamine clearance in the central nervous system. We previously demonstrated that pharmacological inhibition of HNMT markedly elevates brain histamine levels and potently promotes wakefulness in mouse models of narcolepsy and idiopathic hypersomnia, suggesting that targeting HNMT may also be beneficial for treating hypersomnia in PD. Here, we investigated whether pharmacological inhibition of HNMT ameliorates hypersomnia in a 6\u2010hydroxydopamine\u2010induced mouse model of PD. We first confirmed dopaminergic neuronal loss and hypersomnia during the active phase in a mouse model of PD. Pharmacological inhibition of HNMT with metoprine robustly increased wakefulness, markedly reduced NREM and REM sleep, and prolonged sleep latency. Metoprine also reduced sleep\u2013wake bout fragmentation, indicating the sustained consolidation of wakefulness. In direct comparison, metoprine produced stronger and more sustained wake\u2010promoting effects than other wake\u2010promoting agents. These findings indicate that HNMT inhibition represents a promising and mechanistically distinct therapeutic approach for EDS in PD.\n                  <\/jats:p>","DOI":"10.1111\/jsr.70469","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:50:48Z","timestamp":1791931848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Inhibition of Histamine\n                    <i>N<\/i>\n                    \u2010Methyltransferase Markedly Improves Hypersomnia in a Mouse Model of Parkinson's Disease"],"prefix":"10.1111","author":[{"given":"Birkan","family":"Girgin","sequence":"first","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Naganuma","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimasa","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoki","family":"Fujiya","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyosuke","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Ebina","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Morimura","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaho","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Bioregulatory Pharmacology, Department of Pharmacology Iwate Medical University  Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6376-3641","authenticated-orcid":false,"given":"Ramalingam","family":"Vetrivelan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-6021","authenticated-orcid":false,"given":"Takeo","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology Hokkaido University Graduate School of Medicine  Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7362"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1353\u20108020(09)70792\u20108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.25322"},{"issue":"3","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0022-3565(25)28637-2","article-title":"Effect of 6\u2010Hydroxydopamine on Brain Norepinephrine and Dopamine Evidence for Selective Degeneration of Catecholamine Neurons","volume":"174","author":"Breese G. 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