title: Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.
abstract: Epilepsy, a disease characterized by abnormal brain activity, is a disabling and potentially life-threatening condition for nearly 1% of the world population. Unfortunately, modulation of brain excitability using available antiepileptic drugs can have serious side effects, especially in the developing brain, and some patients can only be improved by surgical removal of brain regions containing the seizure focus. Here, we show that bilateral transplantation of precursor cells from the embryonic medial ganglionic eminence (MGE) into early postnatal neocortex generates mature GABAergic interneurons in the host brain. In mice receiving MGE cell grafts, GABA-mediated synaptic and extrasynaptic inhibition onto host brain pyramidal neurons is significantly increased. Bilateral MGE cell grafts in epileptic mice lacking a Shaker-like potassium channel (a gene mutated in one form of human epilepsy) resulted in significant reductions in the duration and frequency of spontaneous electrographic seizures. Our findings suggest that MGE-derived interneurons could be used to ameliorate abnormal excitability and possibly act as an effective strategy in the treatment of epilepsy.
authors.affiliation: Department of Neurological Surgery and Psychiatry, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA. scott.baraban@ucsf.edu
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
authors.forename: Derek G
authors.initials: DG
authors.lastname: Southwell
authors.forename: Rosanne C
authors.initials: RC
authors.lastname: Estrada
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Jones
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Sebe
authors.forename: Clara
authors.initials: C
authors.lastname: Alfaro-Cervello
authors.forename: Jose M
authors.initials: JM
authors.lastname: García-Verdugo
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000818:Animals; D004569:Electroencephalography; D004594:Electrophysiology; D004827:Epilepsy / Q000517:prevention & control / Q000601:surgery*; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology* / Q000637:transplantation; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron
chemical_list: D051662:Kv1.1 Potassium Channel
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