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Neuropeptide Y (NPY) is a 36\u2010amino acid neuropeptide that is expressed primarily by \u03b3\u2010aminobutyric acidergic (GABAergic) interneurons. NPY has widespread effects on the brain, at both the cellular (e.g., reducing excitatory glutamatergic transmission) and circuit levels (e.g., increasing food intake, improving learning and memory, increasing seizure resistance). Previous studies have demonstrated antiseizure effects of NPY following invasive brain delivery methods or gene therapy approaches to increase the expression of NPY or its receptor activity. However, these routes of administration pose challenges for translation into clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To overcome these obstacles, we generated a nanoparticle formulation to encapsulate neuropeptides. In the current study, we evaluated the ability of nanoparticle\u2010encapsulated NPY (NP\u2010NPY) to increase resistance to 6\u2009Hz\u2010, pentylenetetrazole\u2010, and hyperthermia\u2010induced seizures in mouse models of\n                      <jats:italic>SCN1A<\/jats:italic>\n                      \u2010derived epilepsy. We also examined the ability of NP\u2010NPY treatment to protect against spontaneous seizures in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mutant mice, a model of Dravet syndrome. Quantitative reverse transcription polymerase chain reaction was performed to compare expression levels of NPY and its receptors in hippocampi from\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mutants and wild\u2010type littermates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that intranasal NP\u2010NPY administration was able to provide robust protection against induced seizures in two mouse models of\n                      <jats:italic>SCN1A\u2010<\/jats:italic>\n                      derived epilepsy and reduce spontaneous seizure frequency in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mutant mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      These results provide support for further evaluation of NP\u2010NPY as a treatment for\n                      <jats:italic>SCN1A\u2010<\/jats:italic>\n                      derived epilepsy and possibly other epilepsy subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18649","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:06:41Z","timestamp":1760170001000},"page":"424-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanoparticle\u2010encapsulated neuropeptide Y provides robust seizure protection in\n                    <i>SCN1A<\/i>\n                    \u2010derived epilepsy"],"prefix":"10.1111","volume":"67","author":[{"given":"Samantha 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