{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:28:02Z","timestamp":1792052882054,"version":"4.4.0"},"reference-count":114,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSF Graduate Research Fellowship award","award":["NASA NSCOR G-00066-4"],"award-info":[{"award-number":["NASA NSCOR G-00066-4"]}]},{"name":"NSF Graduate Research Fellowship award","award":["R21 CA223461"],"award-info":[{"award-number":["R21 CA223461"]}]},{"name":"NSF Graduate Research Fellowship award","award":["R21 AG065914"],"award-info":[{"award-number":["R21 AG065914"]}]},{"name":"NSF Graduate Research Fellowship award","award":["RF1 AG059088"],"award-info":[{"award-number":["RF1 AG059088"]}]},{"name":"NSF Graduate Research Fellowship award","award":["P30 AG066509"],"award-info":[{"award-number":["P30 AG066509"]}]},{"name":"NSF Graduate Research Fellowship award","award":["NS102227"],"award-info":[{"award-number":["NS102227"]}]},{"name":"NSF Graduate Research Fellowship award","award":["F31 AG067629"],"award-info":[{"award-number":["F31 AG067629"]}]},{"name":"NSF Graduate Research Fellowship award","award":["Knight CVP-003"],"award-info":[{"award-number":["Knight CVP-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA double-strand breaks (DSBs), classified as the most harmful type of DNA damage based on the complexity of repair, lead to apoptosis or tumorigenesis. In aging, DNA damage increases and DNA repair decreases. This is exacerbated in disease, as post-mortem tissue from patients diagnosed with mild cognitive impairment (MCI) or Alzheimer\u2019s disease (AD) show increased DSBs. A novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity leads to increases in DSBs and upregulation of IEGs, while increasing DSBs and inhibiting DSB repair impairs long-term memory and alters IEG expression. Consistent with this pattern, mice carrying dominant AD mutations have increased baseline DSBs, and impaired DSB repair is observed. These data suggest an adaptive role for DSBs in the central nervous system and dysregulation of DSBs and\/or repair might drive age-related cognitive decline (ACD), MCI, and AD. In this review, we discuss the adaptive role of DSBs in hippocampus-dependent learning, memory, and IEG expression. We summarize IEGs, the history of DSBs, and DSBs in synaptic plasticity, aging, and AD. DSBs likely have adaptive functions in the brain, and even subtle alterations in their formation and repair could alter IEGs, learning, and memory.<\/jats:p>","DOI":"10.3390\/ijms23158352","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory"],"prefix":"10.3390","volume":"23","author":[{"given":"Sydney","family":"Weber Boutros","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek K.","family":"Unni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Oregon Health & Science University Parkinson Center, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-9893","authenticated-orcid":false,"given":"Jacob","family":"Raber","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1136\/jnnp.20.1.11","article-title":"Loss of recent memory after bilateral hippocampal lesions","volume":"20","author":"Scoville","year":"1957","journal-title":"J. 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