{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:12:32Z","timestamp":1790158352997,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["T32GM146611"],"award-info":[{"award-number":["T32GM146611"]}]},{"name":"National Institute of Mental Health","award":["7R01MH097949-14"],"award-info":[{"award-number":["7R01MH097949-14"]}]},{"DOI":"10.13039\/100008299","name":"Dartmouth College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008299","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011531","name":"University of Alabama","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011531","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phosphatase and tensin homologue on chromosome 10 (PTEN) is a key negative regulator of the mechanistic target of rapamycin (mTOR) signalling pathway. Mutations in PTEN are highly implicated in autism spectrum disorder, epilepsy, congenital hydrocephaly and macrocephaly. While the conditional genetic knockout of Pten in murine neurons results in hypertrophy, increased migration, excitatory synaptogenesis, hyperexcitability and epileptiform activity, the specific downstream signalling mediators of these pathologies remain to be fully elucidated.<\/jats:p>\n                  <jats:p>Using retroviral-mediated genetic manipulation of individual neurons within the Cre-lox recombination system, we have analysed pathway outputs in response to the manipulation of various genes using immunohistochemistry, confocal microscopy and extensive morphological analyses, alongside whole-cell patch-clamp electrophysiology and 120-h video-EEG monitoring for seizure assessment.<\/jats:p>\n                  <jats:p>Here, we demonstrate that signalling through AKT is necessary for the development of neuronal overgrowth, increased excitatory synapse formation, excessive migration and hyperexcitability fuelled by the loss of PTEN function. Notably, the concurrent deletion of Akt1 and Akt3 isoforms was sufficient to effectively rescue hypertrophic neuronal morphology and physiology.<\/jats:p>\n                  <jats:p>These findings establish AKT as the essential mediator through which PTEN deficiency manifests, providing a transformative therapeutic target to correct the morphological and functional defects central to PTEN-related neurodevelopmental disorders.<\/jats:p>","DOI":"10.1093\/brain\/awag098","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:49:18Z","timestamp":1772887758000},"source":"Crossref","is-referenced-by-count":2,"title":["AKT is necessary for neuronal hypertrophy and epilepsy caused by\n                    <i>Pten<\/i>\n                    knockout"],"prefix":"10.1093","author":[{"given":"Mackenzi L","family":"Prina","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Civitan International Research Center for Neurodevelopmental Disorders, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Goyette","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asan F","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Civitan International Research Center for Neurodevelopmental Disorders, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35294 ,","place":["USA"]},{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Tariq","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Burgess","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute and School of Neuroscience, Virginia Polytechnic and State University , Roanoke, VA 24016 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Su","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute and School of Neuroscience, Virginia Polytechnic and State University , Roanoke, VA 24016 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucky L","family":"Drucker","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena H","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M","family":"Desmet","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Civitan International Research Center for Neurodevelopmental Disorders, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35294 ,","place":["USA"]},{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College , Hanover, NH 03755 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Overstreet-Wadiche","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Civitan International Research Center for Neurodevelopmental Disorders, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Shafit-Zagardo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Weston","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute and School of Neuroscience, Virginia Polytechnic and State University , Roanoke, VA 24016 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan W","family":"Luikart","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Civitan International Research Center for Neurodevelopmental Disorders, University of Alabama at Birmingham Heersink School of Medicine , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"2026092305520880200_awag098-B1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-3-319-27069-2_11","volume-title":"A time for metabolism and 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