{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:18:04Z","timestamp":1777396684379,"version":"3.51.4"},"reference-count":72,"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"}],"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>Individuals with Alzheimer's disease (AD) have a heightened risk of epilepsy. However, the underlying mechanisms are not well-understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to elucidate the role of the glutamate-glutamine cycle in this mechanism and test the effect of ceftriaxone, a glutamate transporter-1 (GLT-1) enhancer, on seizure susceptibility in the Tg2576 mouse model of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      First, we assessed expression levels of key proteins in the glutamate-glutamine cycle in Tg2576 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) and wild-type littermates (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097), and subsequently in the kindling model of epilepsy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) and sham (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096). Then, kindling susceptibility was assessed in three groups: 200\u2005mg\/kg ceftriaxone-treated Tg2576 (Tg-Ceft,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099); saline-treated Tg2576 (Tg-Sal,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099); and saline-treated wild-type (WT-Sal,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915). Mice were treated for seven days before kindling, and seizure susceptibility compared between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Protein levels of GLT-1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0093) and glutamine synthetase (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0016) were reduced in cortex of Tg2576 mice, compared to WT. Kindling increased GLT-1 (cortex:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, hippocampus:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0075), and glutaminase (cortex:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0044) protein levels, compared to sham. Both Tg-Ceft and WT-Sal displayed Class IV seizures in response to the first stimulation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.99), while Tg-Sal displayed Class V seizure (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0212 versus WT-Sal). Seizure susceptibility of Tg-Ceft was not different from Tg-Sal (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05), and kindling rates did not differ between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Disruptions to key components of the glutamate-glutamine cycle are observed in models of AD and epilepsy. However, increasing GLT-1 through ceftriaxone treatment did not influence seizure susceptibility in Tg2576 mice, suggesting this is not an effective strategy to lower seizure susceptibility in AD, or a higher dosage is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241289053","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T01:53:02Z","timestamp":1732499582000},"page":"370-381","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of ceftriaxone on the glutamate-glutamine cycle and seizure susceptibility of Tg2576 mouse model of Alzheimer's disease"],"prefix":"10.1177","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8135-510X","authenticated-orcid":false,"given":"Hattapark","family":"Dejakaisaya","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, 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