{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:59:24Z","timestamp":1763020764201,"version":"3.45.0"},"reference-count":91,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":261,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, we aimed to evaluate the therapeutic effect of levetiracetam (LEV), an antiepileptic drug used in the treatment of both focal and generalized epilepsy, in a propionic acid (PPA)\u2010induced autism model by assessing social deficits, learning and memory impairments, and their neurochemical correlates. We further examined the involvement of the AMPK\/SIRT1 signalling pathway as a potential molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Thirty male Wistar albino rats were allocated into three groups: normal control (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), PPA\u2009+\u2009saline (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and PPA\u2009+\u2009LEV (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910). Autism\u2010like features were induced by intraperitoneal PPA administration (250\u2009mg\/kg\/day, 5\u2009days). LEV was administered orally (100\u2009mg\/kg\/day) for 15\u2009days. Behavioural performance (three\u2010chamber sociability test, open\u2010field test, passive avoidance learning), biochemical markers (malondialdehyde [MDA], tumour necrosis factor\u2010alpha [TNF\u2010\u03b1], brain\u2010derived neurotrophic factor [BDNF], AMPK, and SIRT1) and histopathological changes (neuronal counts in CA1, CA3, Purkinje cells; GFAP immunostaining) were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the sociability test, social interaction time decreased by 51.6% in the PPA\u2009+\u2009saline group compared to controls (67.2%\u2009\u00b1\u20092.4% vs. 32.5%\u2009\u00b1\u20092.1%), while LEV increased it by 121.8% vs. PPA\u2009+\u2009saline (72.1%\u2009\u00b1\u20094.5%). Open\u2010field ambulation decreased by 83% in PPA\u2009+\u2009saline (17.3\u2009\u00b1\u20093.2 vs. 2.9\u2009\u00b1\u20090.8) and increased by 158% with LEV (7.5\u2009\u00b1\u20092.16). Passive avoidance latency decreased by 76% in PPA\u2009+\u2009saline (245.9\u2009\u00b1\u200917.5\u2009s vs. 59.2\u2009\u00b1\u200920.8\u2009s) and increased by 180% with LEV (165.7\u2009\u00b1\u200918.3\u2009s). MDA levels increased by 187% in PPA\u2009+\u2009saline vs. controls (49.9\u2009\u00b1\u20091.4 vs. 143.5\u2009\u00b1\u20094.7\u2009nmol\/g protein) and decreased by 31% with LEV (98.6\u2009\u00b1\u20095.4). TNF\u2010\u03b1 increased by 1012% in PPA\u2009+\u2009saline (13.1\u2009\u00b1\u20090.9 vs. 145.8\u2009\u00b1\u200910.6\u2009pg\/mg protein) and decreased by 39% with LEV (88.4\u2009\u00b1\u20093.9). BDNF decreased by 52% in PPA\u2009+\u2009saline (5.21\u2009\u00b1\u20090.9 vs. 2.48\u2009\u00b1\u20090.3\u2009pg\/mg protein) and increased by 88% with LEV (4.66\u2009\u00b1\u20090.5). AMPK decreased by 62% in PPA\u2009+\u2009saline (113.5\u2009\u00b1\u20096.3 vs. 43.2\u2009\u00b1\u20097.5\u2009pg\/mg protein) and increased by 73% with LEV (74.8\u2009\u00b1\u20092.1). SIRT1 decreased by 75% in PPA\u2009+\u2009saline (4.65\u2009\u00b1\u20090.5 vs. 1.17\u2009\u00b1\u20091.1\u2009pg\/mg protein) and increased by 132% with LEV (2.72\u2009\u00b1\u20090.8). Histologically, CA1 neuronal counts decreased by 35% in PPA\u2009+\u2009saline (67.2\u2009\u00b1\u20092.04 vs. 43.8\u2009\u00b1\u20091.1) and increased by 38% with LEV (60.5\u2009\u00b1\u20091.3). CA3 neuronal counts decreased by 31% in PPA\u2009+\u2009saline (48.5\u2009\u00b1\u20093.2 vs. 33.7\u2009\u00b1\u20091.9) and increased by 31% with LEV (44.2\u2009\u00b1\u20090.8). Purkinje cells decreased by 53% in PPA\u2009+\u2009saline (26.2\u2009\u00b1\u20090.5 vs. 12.2\u2009\u00b1\u20090.8) and increased by 68% with LEV (20.5\u2009\u00b1\u20091.1). GFAP indices in CA1, CA3 and cerebellum were elevated in PPA\u2009+\u2009saline (31.6\u2009\u00b1\u20092.4 vs. 47.5\u2009\u00b1\u20091.2; 33.4\u2009\u00b1\u20091.1 vs. 48.2\u2009\u00b1\u20090.7; 21.2\u2009\u00b1\u20091.6 vs. 32.3\u2009\u00b1\u20090.9) and reduced with LEV (40.3\u2009\u00b1\u20090.6; 39.5\u2009\u00b1\u20090.8; 28.5\u2009\u00b1\u20091.4, respectively).<\/jats:p>\n                    <jats:p>These therapeutic effects were accompanied by marked upregulation of the AMPK\/SIRT1 pathway, which was suppressed in the PPA\u2009+\u2009saline group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LEV treatment ameliorated PPA\u2010induced behavioural, biochemical and histological impairments, likely via anti\u2010inflammatory, antioxidant and neuroprotective mechanisms involving activation of the AMPK\/SIRT1 pathway. These findings support LEV as a potential therapeutic candidate for autism spectrum disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jdn.70055","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:21:36Z","timestamp":1758270096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effect of LEV in a Propionic Acid\u2010Induced Autism Model via AMPK\/SIRT1 Pathway"],"prefix":"10.1002","volume":"85","author":[{"given":"Tar\u0131k","family":"Mecit","sequence":"first","affiliation":[{"name":"Faculty of Medicine, BAMER Biruni University  Istanbul T\u00fcrkiye"},{"name":"Department of Physiology Biruni University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130lknur","family":"Altunta\u015f","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine  Gebze\u2010Kocaeli T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-444X","authenticated-orcid":false,"given":"M\u00fcmin\u00a0Alper","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Katip \u00c7elebi University  Izmir T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-0522","authenticated-orcid":false,"given":"Yi\u011fit","family":"Uyan\u0131kgil","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Ege University  Izmir T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oytun","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, BAMER Biruni University  Istanbul T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45348-z"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2015.07.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jksus.2013.08.006"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00722"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.10.025"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2021.08.005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2010.06.008"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.12.012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20102697(76)90527\u20103"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.50"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.04.381"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743\u20107075\u20108\u201091"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16011312"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldy026"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003905"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192925"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00296"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.08.016"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2005.09.002"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00011"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920211796429745"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.19370"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.5152\/alphapsychiatry.2023.22975"},{"issue":"1","key":"e_1_2_11_26_1","first-page":"35","article-title":"Levetiracetam as an Adjunctive Analgesic in Neoplastic Plexopathies: Case Series and Commentary","volume":"19","author":"Dunteman E. 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