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This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150\u2009mg\/kg\/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10\u2009mg\/kg\/day, p.o) for four weeks, starting from the 7<jats:sup>th<\/jats:sup> week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid \u03b2 42, \u03b2-secretase, and p-tau, while increasing \u03b1-secretase levels. Furthermore, it decreased tumor necrosis factor-\u03b1, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)\/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3\u03b2 (GSK-3\u03b2), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose\/ovariectomy-induced AD-like features through modulation of PI3K\/Akt\/GSK-3\u03b2, Raf-1\/MEK\/ERK, and JNK\/c-Jun pathways.<\/jats:p>","DOI":"10.1038\/s41598-019-46558-1","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T13:50:39Z","timestamp":1562853039000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3\u03b2, and ERK Signalling Pathways"],"prefix":"10.1038","volume":"9","author":[{"given":"Weam W.","family":"Ibrahim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha F.","family":"Abdelkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6831-3124","authenticated-orcid":false,"given":"Hesham M.","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud M.","family":"Khattab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,11]]},"reference":[{"key":"46558_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3389\/fnins.2018.00037","volume":"12","author":"RL Frozza","year":"2018","unstructured":"Frozza, R. 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