{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:51:46Z","timestamp":1781203906000,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation","award":["LQ21H090002"],"award-info":[{"award-number":["LQ21H090002"]}]},{"name":"Zhejiang Provincial Natural Science Foundation","award":["82101392"],"award-info":[{"award-number":["82101392"]}]},{"name":"Zhejiang Provincial Natural Science Foundation","award":["202003N4117"],"award-info":[{"award-number":["202003N4117"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LQ21H090002"],"award-info":[{"award-number":["LQ21H090002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101392"],"award-info":[{"award-number":["82101392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202003N4117"],"award-info":[{"award-number":["202003N4117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ningbo Science and Technology Program","award":["LQ21H090002"],"award-info":[{"award-number":["LQ21H090002"]}]},{"name":"Ningbo Science and Technology Program","award":["82101392"],"award-info":[{"award-number":["82101392"]}]},{"name":"Ningbo Science and Technology Program","award":["202003N4117"],"award-info":[{"award-number":["202003N4117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: D-amino acid oxidase (DAAO) is a flavoenzyme that specifically catalyzes the deamination of many neutral and basic D-amino acids. This study aims to explore the pathological increment of hippocampal DAAO and its potential relationship with delayed hippocampal neuronal death. Methods: Ischemia\u2013reperfusion was induced in mice through middle cerebral artery occlusion (MCAO). Neurological deficit scores and hippocampal neuronal death were assessed in MCAO mice. Immunofluorescent staining was applied to identify activated astrocytes and evaluate DAAO expression. TUNEL and Nissl staining were utilized to identify cell apoptosis of hippocampal neurons. Results: Hippocampal astrocytic DAAO was strikingly increased following ischemic stroke, with the greatest increase on day 5 after surgery, followed by the manifestation of neurobehavioral deficits. Astrocytic DAAO was found to be mainly expressed in the hippocampal CA2 region and linked with subsequent specific neural apoptosis. Thus, it is supposed that the activation of astrocytic DAAO in ischemic stroke might contribute to neuronal death. An intravenous, twice-daily administration of 4H-furo[3,2-b]pyrrole-5-carboxylic acid (SUN, 10 mg\/kg) markedly relieved behavioral status and delayed hippocampal neuronal death by 38.0% and 41.5%, respectively, compared to the model group treated with saline. In transfected primary astrocytes, DAAO overexpression inhibits cell activity, induces cytotoxicity, and promotes hippocampal neuronal death at least partly by enhancing H2O2 levels with subsequent activation of TRP calcium channels in neurons. Conclusions: Our findings suggest that increased hippocampal DAAO is causally associated with the development of delayed neuronal death after MCAO onset via astrocyte\u2013neuron interactions. Hence, targeting DAAO is a promising therapeutic strategy for the management of neurological disorders.<\/jats:p>","DOI":"10.3390\/cells11223689","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:11:21Z","timestamp":1669000281000},"page":"3689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Involvement of DAAO Overexpression in Delayed Hippocampal Neuronal Death"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-4425","authenticated-orcid":false,"given":"Hao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo 315040, China"},{"name":"School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo 315040, China"},{"name":"School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Ye","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo 315040, China"},{"name":"School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo 315040, China"},{"name":"School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo 315040, China"},{"name":"School of Medicine, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1097\/ALN.0b013e3182a66d2a","article-title":"Identification of a novel spinal dorsal horn astroglial D-amino acid oxidase-hydrogen peroxide pathway involved in morphine antinociceptive tolerance","volume":"120","author":"Gong","year":"2014","journal-title":"Anesthesiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1111\/j.1476-5381.2011.01680.x","article-title":"D-Amino acid oxidase-mediated increase in spinal hydrogen peroxide is mainly responsible for formalin-induced tonic pain","volume":"165","author":"Lu","year":"2012","journal-title":"Br. 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