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Thus, we intraventricularly injected acetoacetate into familial AD mice (APPSWE) for 14\u00a0days and monitored their memory and biochemical changes. During the behavior test, acetoacetate at 100\u00a0mg\/kg led to significant improvement in both Y-maze and novel object recognition tests (NORTs) (both P &lt; .05), indicating ameliorating spatial and recognition memory, respectively. Biomedical tests revealed two mechanisms were involved. Firstly, acetoacetate inhibited the GPR43-pERK pathway, which led to apparent inhibition in tumor necrosis factor-\u03b1 and Interleukin-6 expression in the hippocampus in a concentration-dependent manner. Secondarily, acetoacetate stimulated the expression of hippocampal brain-derived neurotrophic factor (BDNF). We concluded that acetoacetate could ameliorate AD symptoms and exhibited promising features as a therapeutic for AD.<\/jats:p>","DOI":"10.1177\/15333175221124949","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T08:05:56Z","timestamp":1663142756000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Acetoacetate Improves Memory in Alzheimer\u2019s Mice via Promoting Brain-Derived Neurotrophic Factor and Inhibiting Inflammation"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-6832","authenticated-orcid":false,"given":"Xiao-Jun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Shanghai Cancer Center, Shanghai Fu-Dan University School of Medicine, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Qin","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Shanghai No. 4 People\u2019s Hospital Affiliated to Shanghai Tongji University School of Medicine, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Shanghai Chang Zheng Hospital, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4206-5374","authenticated-orcid":false,"given":"Bin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Shanghai Cancer Center, Shanghai Fu-Dan University School of Medicine, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"bibr1-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31363-6"},{"key":"bibr2-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"bibr3-15333175221124949","doi-asserted-by":"publisher","DOI":"10.2174\/1872214810666160615102809"},{"key":"bibr4-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1007\/bf03159971"},{"key":"bibr5-15333175221124949","doi-asserted-by":"publisher","DOI":"10.3233\/jad-180707"},{"key":"bibr6-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490050208"},{"key":"bibr7-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01948-5"},{"key":"bibr8-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-4580(03)00087-3"},{"key":"bibr9-15333175221124949","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15092"},{"key":"bibr10-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.10.048"},{"key":"bibr11-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-6-31"},{"key":"bibr12-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2003.09.007"},{"key":"bibr13-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1042\/bj1210017pa"},{"key":"bibr14-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301403200"},{"key":"bibr15-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211609200"},{"key":"bibr16-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0157-3"},{"key":"bibr17-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.04.007"},{"key":"bibr18-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1038\/nature08530"},{"key":"bibr19-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(15)70016-5"},{"key":"bibr20-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912573116"},{"key":"bibr21-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1002\/vms3.356"},{"key":"bibr22-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2009.07.015"},{"key":"bibr23-15333175221124949","volume-title":"The Mouse Brain in Stereotaxic Coodinates","author":"Franklin K","year":"2008"},{"key":"bibr24-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.09.019"},{"key":"bibr25-15333175221124949","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.01.005"},{"key":"bibr26-15333175221124949","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.733607"},{"key":"bibr27-15333175221124949","unstructured":"Abcam. 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