{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T10:39:24Z","timestamp":1764671964385,"version":"3.46.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82325048","82371458"],"award-info":[{"award-number":["82325048","82371458"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to elucidate the molecular role of neuronal nitric oxide synthase (nNOS, encoded by\n                      <jats:italic>Nos1<\/jats:italic>\n                      ) in adult\u2010born dentate granule cells (DGCs) during temporal lobe epilepsy (TLE).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used GFP\u2010expressing retrovirus (RV) to analyze morphological changes in DGCs.\n                      <jats:italic>Nos1<\/jats:italic>\n                      knockout (\n                      <jats:italic>Nos1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice were generated to assess whether nNOS deficiency would induce mossy fiber sprouting (MFS), affect neurogenesis, and observe the morphological changes of DGCs.\n                      <jats:italic>Nos1<\/jats:italic>\n                      conditional knockout (nNOS cKO,\n                      <jats:italic>Nos1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>loxp\/loxp<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice were generated, and pAAV\u2010Nestin\u2010Cre virus was used to selectively delete\n                      <jats:italic>Nos1<\/jats:italic>\n                      in adult\u2010born DGCs, followed by electroencephalogram examination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found seizures induced ectopic location, hilar basal dendrites, and dendritic hypertrophy in DGCs. While nNOS deficiency did not induce abnormal MFS or affect neurogenesis, it caused a significant increase in somatic size, branch points, dendritic length, and spine density in adult\u2010born DGCs. A notable increase in mushroom spine density was observed in the middle and outer 1\/3 of the molecular layer. Selective deletion of\n                      <jats:italic>Nos1<\/jats:italic>\n                      in adult\u2010born DGCs induced epileptic spikes and spontaneous recurrent seizures. Single\u2010nucleus RNA\u2010seq analysis confirmed that newborn neurons in the TLE hippocampus showed reduced nNOS expression and distinct gene expression profiles, likely contributing to abnormal synaptic and dendritic development, as well as increased hippocampal excitability. Single\u2010nucleus RNA\u2010seq analysis further confirmed that newborn neurons in the TLE hippocampus exhibited reduced nNOS expression and distinct gene expression profiles, likely contributing to abnormal synaptic and dendritic development, as well as increased hippocampal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that selective\n                      <jats:italic>Nos1<\/jats:italic>\n                      knockout in adult\u2010born DGCs contributes to epileptogenesis, and regulating nNOS expression may offer a novel therapeutic approach for treating TLE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      Epilepsy is a brain disorder where nerve cells become overly active. We found that deleting a gene called\n                      <jats:italic>Nos1<\/jats:italic>\n                      in adult\u2010born DGCs of mice led to seizures. These cells also showed abnormal shapes and gene activity. Our results suggest that\n                      <jats:italic>Nos1<\/jats:italic>\n                      helps maintain normal brain circuits and could be a new target to treat epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70133","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:15:03Z","timestamp":1756383303000},"page":"1617-1629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deficiency of\n                    <scp>nNOS<\/scp>\n                    in adult\u2010born dentate granule cells causes epilepsy"],"prefix":"10.1002","volume":"10","author":[{"given":"Hanyu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Affiliated Suzhou Hospital of Nanjing Medical University  Suzhou Jiangsu 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