{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:04:17Z","timestamp":1790733857346,"version":"4.1.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,2,16]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Neuronal damage resulting from increased oxidative stress is important in the development of late onset\/age-related Alzheimer\u2019s disease (LOAD). We have developed an oxidative stress\u2013related mouse model of LOAD based on gene deletion of aldehyde dehydrogenase 2 (ALDH2), an enzyme important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit AD-like pathologies and a progressive decline in recognition and spatial memory. This progression presumably has a morphological basis induced by oxidative damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We performed morphometric analyses in the dorsal hippocampal CA1 region (dCA1) to determine if altered neuronal structure can help account for the progressive cognitive impairment in 3- to 12-month-old KO mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Dendritic morphology was quantitatively analyzed by branched structured analysis and Sholl analysis following Golgi-Cox staining in WT mice (148 neurons) versus KO mice (180 neurons).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The morphology and complexity of dCA1 pyramidal neurons were similar at age 3 months in WTs and KOs. However, by 6 months there were significant reductions in apical and basal dendritic length, dendrite complexity, and spine density in KO versus WT mice that were maintained through ages 9 and 12 months. Immunostaining for protein adducts of the lipid peroxidation product 4-hydroxynonenal revealed significant increases in staining in dCA1 (but not ventral CA1) by 3 months, increasing through 12 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This specific and progressive increase in dCA1 oxidative damage preceded detectable synaptic trimming in KO mice, in keeping with studies showing that lesions to dorsal hippocampus primarily impair cognitive memory.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-201024","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T12:19:07Z","timestamp":1610713147000},"page":"1547-1561","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Age-Related Neuronal Deterioration Specifically Within the Dorsal CA1 Region of the Hippocampus in a Mouse Model of Late Onset Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"79","author":[{"given":"Rasha H.","family":"Mehder","sequence":"first","affiliation":[{"name":"Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen\u2019s University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen\u2019s University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. David","family":"Andrew","sequence":"additional","affiliation":[{"name":"Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen\u2019s University, Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.8.759"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.09.001"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.12.007"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.04.009"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1002\/prca.200800161"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.09.027"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-015-0117-y"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101486"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14291"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191067"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.031"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01710-5"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200211000-00006"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1038\/171387a0"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038971"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6142-10.2011"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.8.1088"},{"key":"ref018","first-page":"453","volume":"12","author":"Mehraein P","year":"1975","journal-title":"Adv Neurol"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294247"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1023\/B:NEUR.0000044197.83514.64"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.08.020"},{"key":"ref022","first-page":"435","volume":"1851","author":"Milne GL","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90842-1"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.14997"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.12.008"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812608106"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.12.013"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(05)01024-4"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2011.558092"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1177\/0748233709102209"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.138"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.11.033"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-201024","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-201024","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-201024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:04:48Z","timestamp":1777370688000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-201024"}},"subtitle":[],"editor":[{"given":"Sergio","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1,15]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,2,16]]}},"alternative-id":["10.3233\/JAD-201024"],"URL":"https:\/\/doi.org\/10.3233\/jad-201024","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,15]]}}}