Open AccessChronic partial TrkB activation reduces seizures and mortality in a mouse model of Dravet syndrome
Author(s) -
Feng Gu,
Isabel Parada,
Tao Yang,
Frank M. Longo,
David A. Prince
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022726119
Subject(s) - dravet syndrome , interneuron , tropomyosin receptor kinase b , epilepsy , phenotype , agonist , parvalbumin , neuroscience , encephalopathy , medicine , endocrinology , biology , inhibitory postsynaptic potential , receptor , neurotrophic factors , gene , genetics
Significance Dravet syndrome (DS) is a severe childhood epileptic encephalopathy characterized by intractable seizures and comorbidities, including a high rate of premature mortality. DS is mainly caused by loss-of-function mutations of theScn1a gene encoding sodium channel Nav 1.1 that is predominantly expressed in inhibitory parvalbumin-containing (PV) interneurons. Decreased Nav 1.1 impairs PV cell function, causing DS phenotypes. Effective pharmacological therapy targeting defective PV interneurons is currently not available. This study demonstrated that early treatment with a partial TrkB receptor agonist, LM22A-4, increased Nav 1.1 expression, improved PV interneuron function, and reduced seizure occurrence and mortality rate in DS mice, suggesting a potential therapy for DS.