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However, initial events triggered by A\u03b2O have not been clearly defined. Synaptic (Syn)\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010aspartate receptors (NMDAR) are known to activate cAMP response element\u2010binding protein (CREB), a transcriptional factor involved in gene expression related to cell survival, memory formation and synaptic plasticity, whereas activation of extrasynaptic (ESyn) NMDARs was linked to excitotoxic events. In AD brain, CREB phosphorylation\/activation was shown to be altered, along with dyshomeostasis of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    <jats:sub>i<\/jats:sub>\n                    ). Thus, in this work, we analyze acute\/early and long\u2010term A\u03b2O\u2010mediated changes in CREB activation involving Syn or ESyn NMDARs in mature rat cortical neurons. Our findings show that acute A\u03b2O exposure produce early increase in phosphorylated CREB, reflecting CREB activity, in a process occurring through Syn NMDAR\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx. Data also demonstrate that A\u03b2O long\u2010term (24\u2009h) exposure compromises synaptic function related to Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent CREB phosphorylation\/activation and nuclear CREB levels and related target genes, namely\n                    <jats:italic>Bdnf<\/jats:italic>\n                    ,\n                    <jats:italic>Gadd45\u03b3<\/jats:italic>\n                    ,\n                    <jats:italic>and Btg2<\/jats:italic>\n                    . Data suggest a dual effect of A\u03b2O following early or prolonged exposure in mature cortical neurons through the activation of the CREB signaling pathway, linked to the activation of Syn NMDARs.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16222-fig-0006-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16222","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T09:15:42Z","timestamp":1726132542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Linking activation of synaptic\n                    <scp>NMDA<\/scp>\n                    receptors\u2010induced\n                    <scp>CREB<\/scp>\n                    signaling to brief exposure of cortical neurons to oligomeric amyloid\u2010beta peptide"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6552-4479","authenticated-orcid":false,"given":"I. 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