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However, the earliest role of pre-plaque neuronal oxidative stress, remains elusive. Using laser microdissected hippocampal neurons extracted from McGill-R-Thy1-APP transgenic rats we found that intraneuronal amyloid beta (iA\u03b2)-burdened neurons had increased expression of genes related to oxidative stress and DNA damage responses including\n                    <jats:italic>Ercc2, Fancc, Sod2, Gsr<\/jats:italic>\n                    , and\n                    <jats:italic>Idh1<\/jats:italic>\n                    . DNA damage was further evidenced by increased neuronal levels of XPD (\n                    <jats:italic>Ercc2<\/jats:italic>\n                    ) and \u03b3H2AX foci, indicative of DNA double stranded breaks (DSBs), and by increased expression of\n                    <jats:italic>Ercc6<\/jats:italic>\n                    ,\n                    <jats:italic>Rad51<\/jats:italic>\n                    , and\n                    <jats:italic>Fen1<\/jats:italic>\n                    , and decreased\n                    <jats:italic>Sirt6<\/jats:italic>\n                    in hippocampal homogenates. We also found increased expression of synaptic plasticity genes (\n                    <jats:italic>Grin2b<\/jats:italic>\n                    (NR2B),\n                    <jats:italic>CamkII\u03b1, Bdnf, c-fos<\/jats:italic>\n                    , and\n                    <jats:italic>Homer1A)<\/jats:italic>\n                    and increased protein levels of TOP2\u03b2. Our findings indicate that early accumulation of iA\u03b2, prior to A\u03b2 plaques, is accompanied by incipient oxidative stress and DSBs that may arise directly from oxidative stress or from maladaptive synaptic plasticity.\n                  <\/jats:p>","DOI":"10.1038\/s42003-024-06552-4","type":"journal-article","created":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T06:01:39Z","timestamp":1720936899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Early oxidative stress and DNA damage in A\u03b2-burdened hippocampal neurons in an Alzheimer\u2019s-like transgenic rat model"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9744-1942","authenticated-orcid":false,"given":"Morgan K.","family":"Foret","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Orciani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay A.","family":"Welikovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2143-2745","authenticated-orcid":false,"given":"A. 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