{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:06:14Z","timestamp":1791223574837,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,2]],"date-time":"2013-12-02T00:00:00Z","timestamp":1385942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,3]]},"abstract":"Summary<\/jats:title>Aims<\/jats:title>Previously, we have documented that prenatal hypoxia can aggravate the cognitive impairment and A<\/jats:styled-content>lzheimer's disease (AD<\/jats:styled-content>) neuropathology in APP<\/jats:styled-content>Swe<\/jats:sup>\/PS<\/jats:styled-content>1A246E<\/jats:sup> (APP<\/jats:styled-content>\/PS<\/jats:styled-content>1) transgenic mice, and valproic acid (VPA<\/jats:styled-content>) can prevent hypoxia\u2010induced down\u2010regulation of \u03b2\u2010amyloid (A\u03b2) degradation enzyme neprilysin (NEP<\/jats:styled-content>) in primary neurons. In this study, we have investigated the molecular mechanisms of VPA's anti\u2010AD effects and found that VPA<\/jats:styled-content> can reduce the prenatal hypoxia\u2010induced neuritic plaque formation and improve the learning deficits in the AD mouse model.<\/jats:p><\/jats:sec>Methods<\/jats:title>The pregnant APP<\/jats:styled-content>\/PS<\/jats:styled-content>1 transgenic mice were exposed in a hypobaric chamber. Neuritic plaque staining, Morris water maze, and enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>) were used to detect the effects of VPA<\/jats:styled-content> on A<\/jats:styled-content>\u03b2 neuropathology, learning, and memory. Chromatin immunoprecipitation (C<\/jats:styled-content>hIP<\/jats:styled-content>) assays and real\u2010time PCR<\/jats:styled-content> (RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>) were used to determine the effect of VPA<\/jats:styled-content> on the histone3 acetylation (H<\/jats:styled-content>3\u2010A<\/jats:styled-content>ce).<\/jats:p><\/jats:sec>Results<\/jats:title>We found that VPA<\/jats:styled-content> can inhibit neuritic plaque formation and improve the learning and memory in the prenatal hypoxic APP<\/jats:styled-content>\/PS<\/jats:styled-content>1 transgenic mice. In addition, VPA<\/jats:styled-content> treatment can decrease the soluble and insoluble A<\/jats:styled-content>\u03b242 levels and increase the NEP<\/jats:styled-content> expression via up\u2010regulation of H<\/jats:styled-content>3\u2010A<\/jats:styled-content>ce in the APP<\/jats:styled-content>\/PS<\/jats:styled-content>1 transgenic mice.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Valproic acid is able to attenuate the prenatal hypoxia\u2010induced A\u03b2 neuropathology and learning and memory deficits via inhibiting the activation of histone deacetylase 1 (HDAC<\/jats:styled-content>1), preventing the decrease in H<\/jats:styled-content>3\u2010A<\/jats:styled-content>ce in the NEP<\/jats:styled-content> promoter regions and reducing the down\u2010regulation of NEP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12186","type":"journal-article","created":{"date-parts":[[2013,12,2]],"date-time":"2013-12-02T08:36:37Z","timestamp":1385973397000},"page":"209-217","source":"Crossref","is-referenced-by-count":46,"title":["Valproic Acid Reduces Neuritic Plaque Formation and Improves Learning Deficits in APP<\/scp>Swe<\/sup>\/PS<\/scp>1A246E<\/sup> Transgenic Mice via Preventing the Prenatal Hypoxia\u2010Induced Down\u2010Regulation of Neprilysin"],"prefix":"10.1111","volume":"20","author":[{"given":"Zheng","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Neurology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"State Key Laboratory of Medical Neurobiology Department of Neurology Huashan Hospital Fudan University Shanghai 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