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

Publication ,  Journal Article
Baraban, SC; Southwell, DG; Estrada, RC; Jones, DL; Sebe, JY; Alfaro-Cervello, C; García-Verdugo, JM; Rubenstein, JLR; Alvarez-Buylla, A
Published in: Proc Natl Acad Sci U S A
September 8, 2009

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 8, 2009

Volume

106

Issue

36

Start / End Page

15472 / 15477

Location

United States

Related Subject Headings

  • Microscopy, Electron
  • Mice, Mutant Strains
  • Mice
  • Mesenchymal Stem Cell Transplantation
  • Kv1.1 Potassium Channel
  • Interneurons
  • Immunohistochemistry
  • Epilepsy
  • Electrophysiology
  • Electroencephalography
 

Citation

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MLA
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Baraban, S. C., Southwell, D. G., Estrada, R. C., Jones, D. L., Sebe, J. Y., Alfaro-Cervello, C., … Alvarez-Buylla, A. (2009). Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc Natl Acad Sci U S A, 106(36), 15472–15477. https://doi.org/10.1073/pnas.0900141106
Baraban, Scott C., Derek G. Southwell, Rosanne C. Estrada, Daniel L. Jones, Joy Y. Sebe, Clara Alfaro-Cervello, Jose M. García-Verdugo, John L. R. Rubenstein, and Arturo Alvarez-Buylla. “Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.Proc Natl Acad Sci U S A 106, no. 36 (September 8, 2009): 15472–77. https://doi.org/10.1073/pnas.0900141106.
Baraban SC, Southwell DG, Estrada RC, Jones DL, Sebe JY, Alfaro-Cervello C, et al. Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15472–7.
Baraban, Scott C., et al. “Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.Proc Natl Acad Sci U S A, vol. 106, no. 36, Sept. 2009, pp. 15472–77. Pubmed, doi:10.1073/pnas.0900141106.
Baraban SC, Southwell DG, Estrada RC, Jones DL, Sebe JY, Alfaro-Cervello C, García-Verdugo JM, Rubenstein JLR, Alvarez-Buylla A. Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15472–15477.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 8, 2009

Volume

106

Issue

36

Start / End Page

15472 / 15477

Location

United States

Related Subject Headings

  • Microscopy, Electron
  • Mice, Mutant Strains
  • Mice
  • Mesenchymal Stem Cell Transplantation
  • Kv1.1 Potassium Channel
  • Interneurons
  • Immunohistochemistry
  • Epilepsy
  • Electrophysiology
  • Electroencephalography