{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:12:45Z","timestamp":1790291565992,"version":"4.1.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ4\/01379"],"award-info":[{"award-number":["2018\/31\/B\/NZ4\/01379"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Given the complex etiological basis of Alzheimer\u2019s disease (AD), it is reasonable to hypothesize that neuronal dysfunction and death result from the interplay of numerous factors, both genetic and environmental. Accumulating evidence implicates the immune system and inflammation as key components of the pathomechanism of AD. In the present study, we analyzed the effect of maternal immune activation (MIA) on AD-related pathological changes in middle-aged 12-month-old offspring mice. Additionally, we investigated whether the inhibition of bromodomain and extraterminal domain (BET) proteins, which are readers of the histone acetylation code, could influence these changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In our study, we administered a viral mimetic, polyinosinic-polycytidylic acid (PIC), on gestation day 17 to induce MIA in wild-type C57BL\/6J mice. The BET protein inhibitor, OTX-015 (Birabresib), was administered orally to 12-month-old male offspring for 14 days. Subsequently, behavioral, genetic, and immunochemical analyses were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrated several MIA-evoked molecular alterations in the brains of middle-aged offspring. We observed an increase in <jats:italic>App<\/jats:italic> gene expression (qPCR) and amyloid-<jats:italic>\u03b2<\/jats:italic> (A\u03b2) levels (ELISA), while the levels and phosphorylation of Tau protein remained unchanged (WB). The mRNA levels of selected microglial markers were also elevated in the MIA group. Treatment with OTX-015 improved memory, as observed in the novel object recognition test, and reduced A\u03b2 levels, but did not alter the expression of inflammatory genes or amyloidogenesis-related genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest that inhibition of BET proteins may effectively attenuate neuropathological alterations in the aged brain.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2025.1619583","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T05:26:52Z","timestamp":1752470812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of BET proteins modulates amyloid-beta accumulation and cognitive performance in middle-aged mice prenatally exposed to maternal immune activation"],"prefix":"10.3389","volume":"18","author":[{"given":"Marta","family":"Matuszewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wilkaniec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"G\u0105ssowska-Dobrowolska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Cie\u015blik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Olech-Kocha\u0144czyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Pa\u0142asz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Gawinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Strawski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz A.","family":"Czapski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1093\/brain\/awae216","article-title":"Increases in amyloid-\u03b242 slow cognitive and clinical decline in Alzheimer's disease trials","volume":"147","author":"Abanto","year":"2024","journal-title":"Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e196","DOI":"10.1016\/s2352-3026(16)00021-1","article-title":"Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study","volume":"3","author":"Amorim","year":"2016","journal-title":"Lancet Haematol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.5114\/fn.2014.45562","article-title":"A critical analysis of the 'amyloid cascade hypothesis'","volume":"52","author":"Armstrong","year":"2014","journal-title":"Folia Neuropathol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41592-021-01105-7","article-title":"SNT: a unifying toolbox for quantification of neuronal anatomy","volume":"18","author":"Arshadi","year":"2021","journal-title":"Nat. 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