Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Baraban, SC; Southwell, DG; Estrada, RC; Jones, DL; Sebe, JY; Alfaro-Cervello, C; García-Verdugo, JM; Rubenstein, JLR; Alvarez-Buylla, A

Published Date

  • September 2009

Published In

Volume / Issue

  • 106 / 36

Start / End Page

  • 15472 - 15477

PubMed ID

  • 19706400

Pubmed Central ID

  • 19706400

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0900141106

Language

  • eng