{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:32:59Z","timestamp":1789788779774,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Liaoning Province","award":["20180550468"],"award-info":[{"award-number":["20180550468"]}]},{"name":"Natural Science Foundation of Liaoning Province","award":["LJKZ0830"],"award-info":[{"award-number":["LJKZ0830"]}]},{"name":"Basic Science Foundation of Liaoning Province","award":["20180550468"],"award-info":[{"award-number":["20180550468"]}]},{"name":"Basic Science Foundation of Liaoning Province","award":["LJKZ0830"],"award-info":[{"award-number":["LJKZ0830"]}]},{"name":"Liaoning Provincial Program for Top Discipline of Basic Medical Sciences","award":["20180550468"],"award-info":[{"award-number":["20180550468"]}]},{"name":"Liaoning Provincial Program for Top Discipline of Basic Medical Sciences","award":["LJKZ0830"],"award-info":[{"award-number":["LJKZ0830"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>BG45 is a class \u2160 histone deacetylase inhibitor (HDACI) with selectivity for HDAC3. Our previous study demonstrated that BG45 can upregulate the expression of synaptic proteins and reduce the loss of neurons in the hippocampus of APPswe\/PS1dE9 (APP\/PS1) transgenic mice (Tg). The entorhinal cortex is a pivotal region that, along with the hippocampus, plays a critical role in memory in the Alzheimer\u2019s disease (AD) pathology process. In this study, we focused on the inflammatory changes in the entorhinal cortex of APP\/PS1 mice and further explored the therapeutic effects of BG45 on the pathologies. The APP\/PS1 mice were randomly divided into the transgenic group without BG45 (Tg group) and the BG45-treated groups. The BG45-treated groups were treated with BG45 at 2 months (2 m group), at 6 months (6 m group), or twice at 2 and 6 months (2 and 6 m group). The wild-type mice group (Wt group) served as the control. All mice were killed within 24 h after the last injection at 6 months. The results showed that amyloid-\u03b2 (A\u03b2) deposition and IBA1-positive microglia and GFAP-positive astrocytes in the entorhinal cortex of the APP\/PS1 mice progressively increased over time from 3 to 8 months of age. When the APP\/PS1 mice were treated with BG45, the level of H3K9K14\/H3 acetylation was improved and the expression of histonedeacetylase1, histonedeacetylase2, and histonedeacetylase3 was inhibited, especially in the 2 and 6 m group. BG45 alleviated A\u03b2 deposition and reduced the phosphorylation level of tau protein. The number of IBA1-positive microglia and GFAP-positive astrocytes decreased with BG45 treatment, and the effect was more significant in the 2 and 6 m group. Meanwhile, the expression of synaptic proteins synaptophysin, postsynaptic density protein 95, and spinophilin was upregulated and the degeneration of neurons was alleviated. Moreover, BG45 reduced the gene expression of inflammatory cytokines interleukin-1\u03b2 and tumor necrosis factor-\u03b1. Closely related to the CREB\/BDNF\/NF-kB pathway, the expression of p-CREB\/CREB, BDNF, and TrkB was increased in all BG45 administered groups compared with the Tg group. However, the levels of p-NF-kB\/NF-kB in the BG45 treatment groups were reduced. Therefore, we deduced that BG45 is a potential drug for AD by alleviating inflammation and regulating the CREB\/BDNF\/NF-kB pathway, and the early, repeated administration of BG45 can play a more effective role.<\/jats:p>","DOI":"10.3390\/ijms24054805","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T03:29:00Z","timestamp":1677727740000},"page":"4805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Selective Targeting of Class I HDAC Reduces Microglial Inflammation in the Entorhinal Cortex of Young APP\/PS1 Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Chunyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqiu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangwei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Oncology, Dalian Municipal Central Hospital, Dalian 116089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dalian Municipal Central Hospital, Dalian 116089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jalz.2014.12.007","article-title":"Alzheimer\u2019s disease first symptoms are age dependent: Evidence from the NACC dataset","volume":"11","author":"Barnes","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2020). 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