{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:27:40Z","timestamp":1791570460990,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018\/02559"],"award-info":[{"award-number":["2018\/02559"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["FO2020\u20100038"],"award-info":[{"award-number":["FO2020\u20100038"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["# 2019.0467"],"award-info":[{"award-number":["# 2019.0467"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["# 2019.0467"],"award-info":[{"award-number":["# 2019.0467"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001232","name":"Royal Australasian College of Physicians","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008714","name":"Motor Neurone Disease Research Institute of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008714","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001773","name":"University of New South Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001773","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine the underlying cellular changes and clinical correlates associated with pathology of the hypothalamus in amyotrophic lateral sclerosis (ALS), as hypothalamic atrophy occurs in the preclinical phase of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The hypothalamus was pathologically examined in nine patients with amyotrophic lateral sclerosis in comparison to eight healthy control subjects. The severity of regional atrophy (paraventricular nucleus: PVN, fornix and total hypothalamus) and peptidergic neuronal loss (oxytocin, vasopressin, cocaine\u2010 and amphetamine\u2010regulating transcript: CART, and orexin) was correlated with changes in eating behaviour, sleep function, cognition, behaviour and disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tar DNA\u2010binding protein 43 (TDP\u201043) inclusions were present in the hypothalamus of all patients with amyotrophic lateral sclerosis. When compared to controls, there was atrophy of the hypothalamus (average 21% atrophy,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.004), PVN (average 30% atrophy\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.014) and a loss of paraventricular oxytocin\u2010producing neurons (average 49% loss\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02) and lateral hypothalamic orexin\u2010producing neurons (average 37% loss, significance\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02). Factor analysis identified strong relationships between abnormal eating behaviour, hypothalamic atrophy and loss of orexin\u2010producing neurons. With increasing disease progression, abnormal sleep behaviour and cognition associated with atrophy of the fornix.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Substantial loss of hypothalamic oxytocin\u2010producing neurons occurs in ALS, with regional atrophy and the loss of orexin neurons relating to abnormal eating behaviour in ALS. Oxytocin\u2010 and orexin neurons display TDP43 inclusions. Our study points to significant pathology in the hypothalamus that may play a key role in metabolic and pathogenic changes in ALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12709","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T13:25:31Z","timestamp":1616505931000},"page":"979-989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Loss of the metabolism and sleep regulating neuronal populations expressing orexin and oxytocin in the hypothalamus in amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"47","author":[{"given":"Sanaz","family":"Gabery","sequence":"first","affiliation":[{"name":"Translational Neuroendocrine Research Unit Department of Experimental Medical Science Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-8317","authenticated-orcid":false,"given":"Rebekah M","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Memory and Cognition Clinic Department of Clinical Neurosciences Royal Prince Alfred Hospital  Sydney NSW Australia"},{"name":"Brain &amp; Mind Centre and Faculty of Medicine and Health The University of Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jashelle","family":"Caga","sequence":"additional","affiliation":[{"name":"Brain &amp; Mind Centre and Faculty of Medicine and Health The University of Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Memory and Cognition Clinic Department of Clinical Neurosciences Royal Prince Alfred Hospital  Sydney NSW Australia"},{"name":"Brain &amp; Mind Centre and Faculty of Medicine and Health The University of Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0422-8398","authenticated-orcid":false,"given":"Glenda M","family":"Halliday","sequence":"additional","affiliation":[{"name":"Brain &amp; Mind Centre and Faculty of Medicine and Health School of Medical Sciences The University of Sydney  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5488-1200","authenticated-orcid":false,"given":"\u00c5sa","family":"Peters\u00e9n","sequence":"additional","affiliation":[{"name":"Translational Neuroendocrine Research Unit Department of Experimental Medical Science Lund University  Lund 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