<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> . <> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/AcademicArticle> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/title> "Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/abstract> "Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/date> "2022-01-10" . <https://discovery-pp.ucl.ac.uk/id/document/1437300> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Document> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/volume> "13" . <https://discovery-pp.ucl.ac.uk/id/publication/ext-93ad60708ded9f1ac36bc6a921129f1f> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Collection> . <https://discovery-pp.ucl.ac.uk/id/publication/ext-93ad60708ded9f1ac36bc6a921129f1f> <http://xmlns.com/foaf/0.1/name> "Nature Communications"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/isPartOf> <https://discovery-pp.ucl.ac.uk/id/publication/ext-93ad60708ded9f1ac36bc6a921129f1f> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/status> <http://purl.org/ontology/bibo/status/published> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-68aa36a894915894c2d74f742552301f> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery-pp.ucl.ac.uk/id/person/ext-68aa36a894915894c2d74f742552301f> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-abc2929d360fba85a2bb39c21c393e06> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_2> <https://discovery-pp.ucl.ac.uk/id/person/ext-abc2929d360fba85a2bb39c21c393e06> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_3> <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_4> <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-033872da4e2a732381da7542a20cc475> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_5> <https://discovery-pp.ucl.ac.uk/id/person/ext-033872da4e2a732381da7542a20cc475> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-b9749daa7ff4dcc5723ede4706a5bc97> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_6> <https://discovery-pp.ucl.ac.uk/id/person/ext-b9749daa7ff4dcc5723ede4706a5bc97> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_7> <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_8> <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_9> <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-6a546d76a23e853d23c8bad16eee3d46> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_10> <https://discovery-pp.ucl.ac.uk/id/person/ext-6a546d76a23e853d23c8bad16eee3d46> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_11> <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_12> <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-bb56297b181f3e607d275133a7c00513> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_13> <https://discovery-pp.ucl.ac.uk/id/person/ext-bb56297b181f3e607d275133a7c00513> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/dc/terms/creator> <https://discovery-pp.ucl.ac.uk/id/person/ext-715fa138e394914a927e1d46a44e2cee> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555> <http://purl.org/ontology/bibo/authorList> <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> . <https://discovery-pp.ucl.ac.uk/id/eprint/10142555#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_14> <https://discovery-pp.ucl.ac.uk/id/person/ext-715fa138e394914a927e1d46a44e2cee> . <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> <http://xmlns.com/foaf/0.1/givenName> "G"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> <http://xmlns.com/foaf/0.1/familyName> "Lignani"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-55dcab3ae671e73f7d653464eae5dcfe> <http://xmlns.com/foaf/0.1/name> "G Lignani"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> <http://xmlns.com/foaf/0.1/givenName> "S"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> <http://xmlns.com/foaf/0.1/familyName> "Bido"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b88688bb281472e1fee968d9aebf24c4> <http://xmlns.com/foaf/0.1/name> "S Bido"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> <http://xmlns.com/foaf/0.1/givenName> "A"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> <http://xmlns.com/foaf/0.1/familyName> "Salamone"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-5feb327f13abbde7f0c2b5f197c7628d> <http://xmlns.com/foaf/0.1/name> "A Salamone"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> <http://xmlns.com/foaf/0.1/givenName> "F"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> <http://xmlns.com/foaf/0.1/familyName> "Ungaro"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-b4c0033fe5dc072558a9dda8b8e30cbf> <http://xmlns.com/foaf/0.1/name> "F Ungaro"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> <http://xmlns.com/foaf/0.1/givenName> "P"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> <http://xmlns.com/foaf/0.1/familyName> "D'Adamo"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-e1970306b56b2ec9f5961cde494e3a63> <http://xmlns.com/foaf/0.1/name> "P D'Adamo"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> <http://xmlns.com/foaf/0.1/givenName> "L"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> <http://xmlns.com/foaf/0.1/familyName> "Massimino"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-f14765e77bde3ebb683e627b4896b9e3> <http://xmlns.com/foaf/0.1/name> "L Massimino"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> <http://xmlns.com/foaf/0.1/givenName> "L"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> <http://xmlns.com/foaf/0.1/familyName> "Serra"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-7664e8809eb7f366cac4b4cb7406e654> <http://xmlns.com/foaf/0.1/name> "L Serra"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery-pp.ucl.ac.uk/id/person/ext-033872da4e2a732381da7542a20cc475> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery-pp.ucl.ac.uk/id/person/ext-033872da4e2a732381da7542a20cc475> <http://xmlns.com/foaf/0.1/givenName> "M"^^<http://www.w3.org/2001/XMLSchema#string> . 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