{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:32:12Z","timestamp":1782948732144,"version":"3.54.5"},"reference-count":18,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Diabetes mellitus (DM) is a risk factor for Alzheimer\u2019s disease (AD). Increasing evidence indicates that the triggering receptor expressed on myeloid cells (TREM)-1 amplifies chronic inflammation, as well as the roles of prolactin (PRL) and metformin (MET) in tau hyperphosphorylation. However, the associations among TREM-1, tau hyperphosphorylation, PRL expression, and MET in DM remain unclear. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Streptozotocin was used to induce experimental DM in C57BL\/6N mice. MET was orally administered at a dose of 400 mg\/kg body weight for 6 weeks prior to hippocampal collection in DM mice. Various parameters pertaining to the TREM-1 pathway, tau hyperphosphorylation, PRL, and related factors were analyzed. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Quantitative polymerase chain reaction and Western blot analysis demonstrated that the expression levels of TREM-1, DAP12, casp1, interleukin-1\u03b2, Cox2, inducible nitric oxide synthase, pituitary transcriptional factor-1 (Pit-1), and PRL were significantly increased in the hippocampus of DM mice; the expression levels of these pro-inflammatory mediators, PRL receptor (PRLR) short or long (PRLR-S and PRLR-L), and PRL regulatory element-binding (Preb) protein in DM mice treated with MET (DM + MET) were significantly decreased compared with those in control (CON) mice. The levels of p-Tau and glycogen synthase kinase-3 in the DM group were significantly higher than those in the CON group and significantly lower than those in the DM + MET group. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; We confirmed the therapeutic potential of MET for both DM and neurodegeneration. Our findings shed new light on the effects of DM on the pathophysiology of AD via the TREM-1 pathway and PRL expression. Thus, an improved understanding of the TREM-1 pathway in hyperglycemic conditions, as well as PRL, Preb, Pit-1, PRLR-L, and PRLR-S gene expression in the liver, brain, and other sites, may help unravel the pathogenesis of insulin resistance and neurodegeneration. <\/jats:p>","DOI":"10.1159\/000521013","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T22:00:42Z","timestamp":1644271242000},"page":"359-368","source":"Crossref","is-referenced-by-count":14,"title":["Associations among the TREM-1 Pathway, Tau Hyperphosphorylation, Prolactin Expression, and Metformin in Diabetes Mice"],"prefix":"10.1159","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8419-7784","authenticated-orcid":false,"given":"Hai","family":"Duc Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Minh Hong","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6875-4050","authenticated-orcid":false,"given":"Won Hee","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Ri","family":"Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9952-0038","authenticated-orcid":false,"given":"Min Sun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60360-2"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.5.661"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150820"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6823-13-12"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.4.0260"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/35074114"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.8.1111"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.043"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.08.036"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.50"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.12.004"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2007.11.021"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0204-y"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.03.024"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0171"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.01.018"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0695"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.03.002"}],"container-title":["Neuroimmunomodulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/521013","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/521013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:35:39Z","timestamp":1745422539000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000521013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":18,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,12,13]]},"published-print":{"date-parts":[[2022,12,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000521013","archive":["Portico"],"relation":{},"ISSN":["1021-7401","1423-0216"],"issn-type":[{"value":"1021-7401","type":"print"},{"value":"1423-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}