Nanoparticle encapsulated oxytocin increases resistance to induced seizures and restores social behavior in Scn1a-derived epilepsy

• Type of Material: Article
• Authors: Jennifer Wong, Emory University; Lindsey Shapiro, Emory University; Jacquelyn T. Thelin, Emory University; Elizabeth C. Heaton, Emory University; Rokon U. Zaman, Mercer University; Martin J. D'Souza, Mercer University; Kevin S. Murnane, Mercer University; Andrew Escayg, Emory University
• Language: English
• Date: 2021-01-01
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nbd.2020.105147
• Title of Journal or Parent Work: NEUROBIOLOGY OF DISEASE
• Volume: 147
• Start Page: 105147
• End Page: 105147
• Grant/Funding Information: This study was supported in part by the National Institutes of Health (R21NS114795 JCW; AE and KSM, R21NS100512; KSM, DA046215) and the American Epilepsy Society (LS). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.
• Keywords: Life Sciences & Biomedicine; Neurosciences; NEUROPEPTIDE-Y; RECEPTOR AGONISTS; Nanoparticles; SEVERE MYOCLONIC EPILEPSY; MOUSE MODEL; Oxytocin; MELANOTAN-II; NEURONAL SODIUM-CHANNEL; Scn1a; Behavior; GENERALIZED EPILEPSY; Science & Technology; CHITOSAN NANOPARTICLES; Neurosciences & Neurology; CHANNEL ALPHA-1-SUBUNIT MUTATIONS; Seizure; RAT HIPPOCAMPUS
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

Abstract

Oxytocin (OT) has broad effects in the brain and plays an important role in cognitive, social, and neuroendocrine function. OT has also been identified as potentially therapeutic in neuropsychiatric disorders such as autism and depression, which are often comorbid with epilepsy, raising the possibility that it might confer protection against the behavioral and seizure phenotypes in epilepsy. Dravet syndrome (DS) is an early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), treatment-resistant afebrile epilepsy, and cognitive and behavioral deficits. De novo loss-of-function mutations in the voltage-gated sodium channel SCN1A are the main cause of DS, while genetic epilepsy with febrile seizures plus (GEFS+), also characterized by early-life FSs and afebrile epilepsy, is typically caused by inherited mutations that alter the biophysical properties of SCN1A. Despite the wide range of available antiepileptic drugs, many patients with SCN1A mutations do not achieve adequate seizure control or the amelioration of associated behavioral comorbidities. In the current study, we demonstrate that nanoparticle encapsulation of OT conferred robust and sustained protection against induced seizures and restored more normal social behavior in a mouse model of Scn1a-derived epilepsy. These results demonstrate the ability of a nanotechnology formulation to significantly enhance the efficacy of OT. This approach will provide a general strategy to enhance the therapeutic potential of additional neuropeptides in epilepsy and other neurological disorders.