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We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a\u2009\u00b1\u2009mice, a murine model of Dravet Syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a\u2009\u00b1\u2009mice. By crossing Scn1a\u2009\u00b1\u2009mice with eEF2K\u2212\/\u2212 mice we obtained the three main genotypes needed for our studies, Scn1a+\/+ eEF2K+\/+ (WT mice), Scn1a\u2009\u00b1\u2009eEF2K+\/+ mice (Scn1a\u2009\u00b1\u2009mice) and Scn1a\u2009\u00b1\u2009eEF2K\u2212\/\u2212 mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a\u2009\u00b1\u2009mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We showed that the activity of eEF2K\/eEF2 pathway was enhanced in Scn1a\u2009\u00b1\u2009mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a\u2009\u00b1\u2009mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a\u2009\u00b1\u2009mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K\/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a\u2009\u00b1\u2009needs further investigations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13229-021-00484-0","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T05:04:48Z","timestamp":1641186288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K)"],"prefix":"10.1186","volume":"13","author":[{"given":"Stefania","family":"Beretta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gritti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Ponzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Scalmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mantegazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaelvina","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Verpelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0662-9523","authenticated-orcid":false,"given":"Carlo","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"issue":"3","key":"484_CR1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.yebeh.2011.11.022","volume":"23","author":"AC Bender","year":"2012","unstructured":"Bender AC, Morse RP, Scott RC, Holmes GL, Lenck-Santini PP. 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