{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:31:31Z","timestamp":1777397491133,"version":"3.51.4"},"reference-count":57,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG057767"],"award-info":[{"award-number":["R01AG057767"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG061937"],"award-info":[{"award-number":["R01AG061937"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dale and Deborah Smith Center for Alzheimer\u2019s Research and Treatment"},{"name":"Kenneth Stark Endowment"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APP\n                      <jats:sup>NL-F\/NL--F<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      At 2\u20134 and 18+ months old, male and female APP\n                      <jats:sup>NL\/NL<\/jats:sup>\n                      , APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      , and C57BL\/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippocampus using a glutamate-selective microelectrode in anesthetized mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Glutamate recordings support elevated stimulus-evoked glutamate release in the DG and CA3 of young APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      male mice that declined with age compared to age-matched control mice. Young female APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      mice exhibited increased glutamate clearance in the CA1 that slowed with age compared to age-matched control mice. Male and female APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      mice exhibited decreased CA1 basal glutamate levels, while males also showed depletion in the CA3. Cognitive assessment demonstrated impaired spatial cognition in aged male and female APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      mice, but only aged females displayed recognition memory deficits compared to age-matched control mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings confirm a sex-dependent hyper-to-hypoactivation glutamatergic paradigm in APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      mice. Further, data illustrate a sexually dimorphic biological aging process resulting in a more severe cognitive phenotype for female APP\n                      <jats:sup>NL-F\/NL-F<\/jats:sup>\n                      mice than their male counterparts. Research outcomes mirror that of human AD pathology and provide further evidence of divergent AD pathogenesis between sexes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-240795","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T09:06:29Z","timestamp":1733216789000},"page":"491-505","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Sexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice"],"prefix":"10.1177","volume":"102","author":[{"given":"Caleigh A","family":"Findley","sequence":"first","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"},{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel A","family":"McFadden","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiarra","family":"Hill","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie R","family":"Peck","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Quinn","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin N","family":"Hascup","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"},{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA"},{"name":"Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-0809","authenticated-orcid":false,"given":"Erin R","family":"Hascup","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Dale and Deborah Smith Center for Alzheimer's Research and Treatment, Departments of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA"},{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"e_1_3_5_2_2","volume-title":"Neuroscience","author":"Purves D","year":"2001","unstructured":"Purves D, Augustine GJ, Fitzpatrick D, et al. Glutamate. In: Neuroscience. 2nd ed. Sunderland, MA: Sinauer Associates, 2001, Chapter 6.","edition":"2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02253527"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(00)00225-6"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.929474"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.654931"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00469"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv007"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1397-18.2018"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50333"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.08.027"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19442-7"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.03.008"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02057.x"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/1533317511421780"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22607"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71587-6"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1759091419855541"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1997.00550220042012"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.07.013"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3697"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.07.001"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24657-9"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210629"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83851-4"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142160"},{"key":"e_1_3_5_27_2","first-page":"407","volume-title":"Electrochemical Methods for Neuroscience","author":"Hascup KN","year":"2007","unstructured":"Hascup KN, Rutherford EC, Quintero JE, et al. Second-by-second measures of L-glutamate and other neurotransmitters using enzyme-based microelectrode arrays. In: Electrochemical Methods for Neuroscience. Boca Raton (FL): CRC Press\/Taylor & Francis, 2007, pp.407\u2013450."},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2014.0423"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.110190"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00343.2011"},{"key":"e_1_3_5_31_2","first-page":"700","article-title":"2022 Alzheimer\u2019s disease facts and figures","author":"Alzheimer\u2019s Association","unstructured":"Alzheimer\u2019s Association. 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 2022; 18: 700\u2013789.","journal-title":"Alzheimers Dement"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2016.18.4\/cepperson"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.5498\/wjp.v6.i1.54"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-06637-2"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2011.08.003"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-011-9691-4"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160041"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26888-2"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304171110"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-016-0248-3"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142367"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.03.012"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111473"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2007.08.006"},{"key":"e_1_3_5_45_2","first-page":"1346","article-title":"Estrogen and progesterone attenuate glutamate neurotoxicity via regulation of EAAT3 and GLT-1 in a rat model of ischemic stroke","volume":"23","author":"Nematipour S","year":"2020","unstructured":"Nematipour S, Vahidinia Z, Nejati M, et al. Estrogen and progesterone attenuate glutamate neurotoxicity via regulation of EAAT3 and GLT-1 in a rat model of ischemic stroke. Iran J Basic Med Sci 2020; 23: 1346\u20131352.","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65402-5"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2019.03.013"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05147.x"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-015-9589-x"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13429"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180410"},{"key":"e_1_3_5_52_2","first-page":"14","article-title":"Sex and gender differences in Alzheimer disease dementia","volume":"35","author":"Mielke MM","year":"2018","unstructured":"Mielke MM. Sex and gender differences in Alzheimer disease dementia. Psychiatr Times 2018; 35: 14\u201315.","journal-title":"Psychiatr Times"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.918309"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0179-5"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.03.010"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00037"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24123"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-240795","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-240795","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-240795","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:10:58Z","timestamp":1777371058000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-240795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.3233\/JAD-240795"],"URL":"https:\/\/doi.org\/10.3233\/jad-240795","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.05.570100","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]}}}