{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:09:19Z","timestamp":1788966559317,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Research has implicated disrupted autophagy initiation in the pathophysiology of depression. However, the role of Unc-51-like Kinase 1 (ULK1), a key regulator of autophagy initiation, in depression remains poorly understood.<\/jats:p>\n                  <jats:p>Here, using behavioural, molecular, and genetic approaches, we show that serum ULK1 levels are decreased in both patients with depression and mice susceptible to chronic social-defeat stress, and that both ULK1 and p-ULK1 (Ser-555) are downregulated in the lateral habenula (LHb) of susceptible mice. In addition, ULK1 deficiency in the LHb is sufficient to induce depressive-like behaviours in mice. Conversely, restoration of ULK1 in the LHb, either genetically or pharmacologically, produced antidepressant-like effects. Moreover, ULK1 deficiency specifically in LHb glutamatergic neurons induces neuronal hyperactivity, which contributes to ULK1 deficiency-induced depressive-like behaviours. Mechanistically, LHb glutamatergic neuron-specific ULK1 deficiency upregulates ryanodine receptor 2 (RYR2), which mediates increased stress-evoked presynaptic calcium transients, enhances presynaptic glutamatergic transmission, and neuronal hyperactivity in the LHb, ultimately resulting in depressive-like behaviours.<\/jats:p>\n                  <jats:p>Collectively, our findings suggest that ULK1 deficiency in LHb glutamatergic neurons may contribute to the development and progression of depression and identify ULK1 as a potential target for further investigation in antidepressant therapy development.<\/jats:p>","DOI":"10.1093\/brain\/awag298","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:35:04Z","timestamp":1788867304000},"source":"Crossref","is-referenced-by-count":0,"title":["ULK1 inhibits depressive behaviours by reversing RYR2-mediated hyperactivity in lateral habenula"],"prefix":"10.1093","author":[{"given":"Pingjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Department of Neurology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Department of Microbiology and Immunology, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boya","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedical Sciences, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenghei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhe","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikias","family":"Siafarikas","sequence":"additional","affiliation":[{"name":"Department of Geriatric Psychiatry, Akershus University Hospital , L\u00f8renskog, 1478 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tormod","family":"Fladby","sequence":"additional","affiliation":[{"name":"Department of Neurology, Akershus University Hospital , L\u00f8renskog, 1478 ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, Campus Ahus, University of Oslo , Oslo, 0318 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital , L\u00f8renskog, 1478 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar Junhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Systems Biomedical Sciences, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital, Zhengzhou University , Zhengzhou, 450052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Nanophotonic Manipulation, Institute of Nanophotonics, College of Physics & Optoelectronic Engineering, Jinan University , Guangzhou, 511443 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-6867","authenticated-orcid":false,"given":"Ji-chun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"generation Institute, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, Jinan University \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoran","family":"Ren","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"generation Institute, Key Laboratory of \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"generation (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, Jinan University \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education , Guangzhou, 510632 ,","place":["China"]},{"name":"Zhuhai Institute of Jinan University, Jinan University , Zhuhai, 519070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evandro Fei","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital , L\u00f8renskog, 1478 ,","place":["Norway"]},{"name":"Department of Geriatrics, The First Affiliated Hospital, Zhengzhou University , Zhengzhou, 450052 ,","place":["China"]},{"name":"The Norwegian Centre on Healthy Ageing (NO-Age) and the Norwegian National Anti-Alzheimer's Disease (NO-AD) Networks , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology, The First Affiliated Hospital of Jinan University, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Guangdong-Hongkong-Macau \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"generation Institute, Key Laboratory of \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"generation (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, Jinan University \u00a0 CNS Re \u00a0 CNS Re , Guangzhou, 510632 ,","place":["China"]},{"name":"Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University , Guangzhou, 510632 ,","place":["China"]},{"name":"Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education , Guangzhou, 510632 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