title: Transplantation of GABAergic Interneurons into the Neonatal Primary Visual Cortex Reduces Absence Seizures in Stargazer Mice.
abstract: Epilepsies are debilitating neurological disorders characterized by repeated episodes of pathological seizure activity. Absence epilepsy (AE) is a poorly understood type of seizure with an estimated 30% of affected patients failing to respond to antiepileptic drugs. Thus, novel therapies are needed for the treatment of AE. A promising cell-based therapeutic strategy is centered on transplantation of embryonic neural stem cells from the medial ganglionic eminence (MGE), which give rise to gamma-aminobutyric acidergic (GABAergic) interneurons during embyronic development. Here, we used the Stargazer (Stg) mouse model of AE to map affected loci using c-Fos immunohistochemistry, which revealed intense seizure-induce activity in visual and somatosensory cortices. We report that transplantation of MGE cells into the primary visual cortex (V1) of Stg mice significantly reduces AE episodes and lowers mortality. Electrophysiological analysis in acute cortical slices of visual cortex demonstrated that Stg V1 neurons exhibit more pronounced increases in activity in response to a potassium-mediated excitability challenge than wildtypes (WT). The defective network activity in V1 was significantly altered following WT MGE transplantation, associating it with behavioral rescue of seizures in Stgs. Taken together, these findings present MGE grafting in the V1 as a possible clinical approach in the treatment of AE.
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hammad
authors.affiliation: UNC Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Schmidt
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine.
authors.forename: Xuying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bray
authors.affiliation: UNC Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Frohlich
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine Program in Genetics, North Carolina State University, Raleigh, NC 27607, USA.
authors.forename: H Troy
authors.initials: HT
authors.lastname: Ghashghaei
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D004832:Epilepsy, Absence / Q000235:genetics / Q000601:surgery*; D059330:GABAergic Neurons / Q000502:physiology / Q000637:transplantation*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008473:Median Eminence / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016896:Treatment Outcome; D014793:Visual Cortex / Q000637:transplantation*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase
keywords: MGE transplantation; Stargazer; absence seizure; network activity; visual cortex