{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:58:05Z","timestamp":1781978285436,"version":"3.54.5"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A6A3A01096433"],"award-info":[{"award-number":["NRF-2020R1A6A3A01096433"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["National Research Foundation of Korea"],"award-info":[{"award-number":["National Research Foundation of Korea"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hallym University Research Fund","award":["HRF-202012-015"],"award-info":[{"award-number":["HRF-202012-015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Severe hypoglycemia (below 35 mg\/dL) appears most often in diabetes patients who continuously inject insulin. To rapidly cease the hypoglycemic state in this study, glucose reperfusion was conducted, which can induce a secondary neuronal death cascade following hypoglycemia. Acid sphingomyelinase (ASMase) hydrolyzes sphingomyelin into ceramide and phosphorylcholine. ASMase activity can be influenced by cations, pH, redox, lipids, and other proteins in the cells, and there are many changes in these factors in hypoglycemia. Thus, we expect that ASMase is activated excessively after hypoglycemia. Ceramide is known to cause free radical production, excessive inflammation, calcium dysregulation, and lysosomal injury, resulting in apoptosis and the necrosis of neurons. Imipramine is mainly used in the treatment of depression and certain anxiety disorders, and it is particularly known as an ASMase inhibitor. We hypothesized that imipramine could decrease hippocampal neuronal death by reducing ceramide via the inhibition of ASMase after hypoglycemia. In the present study, we confirmed that the administration of imipramine significantly reduced hypoglycemia-induced neuronal death and improved cognitive function. Therefore, we suggest that imipramine may be a promising therapeutic tool for preventing hypoglycemia-induced neuronal death.<\/jats:p>","DOI":"10.3390\/cells11040667","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T20:26:42Z","timestamp":1644870402000},"page":"667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Administration of an Acidic Sphingomyelinase (ASMase) Inhibitor, Imipramine, Reduces Hypoglycemia-Induced Hippocampal Neuronal Death"],"prefix":"10.3390","volume":"11","author":[{"given":"A Ra","family":"Kho","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-3503","authenticated-orcid":false,"given":"Bo Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Ki","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beom Seok","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Won","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Kangwon-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. 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