Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice.
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.
Baraban
Scott C
SC
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
Southwell
Derek G
DG
Estrada
Rosanne C
RC
Jones
Daniel L
DL
Sebe
Joy Y
JY
Alfaro-Cervello
Clara
C
García-Verdugo
Jose M
JM
Rubenstein
John L R
JL
Alvarez-Buylla
Arturo
A
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
D051662:Kv1.1 Potassium Channel
J Neurosci Res. 1998 Jan 15;51(2):196-209
9469573
Brain Res. 1989 Aug 28;495(2):387-95
2569920
Nat Neurosci. 1999 May;2(5):461-6
10321251
J Neurophysiol. 1969 Sep;32(5):663-87
4309022
Neurobiol Dis. 2007 Aug;27(2):117-32
17618126
Neuroscience. 2005;133(4):1029-37
15927406
Exp Neurol. 2000 Feb;161(2):481-9
10686070
J Neurosci. 2004 Mar 24;24(12):3051-9
15044544
Mol Ther. 2007 Jun;15(6):1106-13
17387333
Mol Ther. 2006 Jul;14(1):63-8
16730475
Neuropsychologia. 1990;28(6):627-34
2168529
Nat Neurosci. 2007 Dec;10(12):1554-8
17982453
Exp Neurol. 2002 Jul;176(1):183-92
12093095
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7611-6
11404469
Epilepsia. 2007 Nov;48(11):2023-46
17651419
Neuron. 1998 Apr;20(4):809-19
9581771
J Neurosci. 2006 Jul 12;26(28):7380-9
16837585
Nat Med. 2003 Aug;9(8):1076-80
12858168
Neurology. 1998 Jan;50(1):27-36
9443453
J Neurosci Res. 2008 Feb 15;86(3):512-24
17918739
J Neurosci. 2005 Sep 14;25(37):8391-401
16162921
Novartis Found Symp. 2007;288:21-35; discussion 35-44, 96-8
18494250
Hippocampus. 2007;17(10):943-56
17604349
Brain. 2007 May;130(Pt 5):1276-88
17472985
Exp Neurol. 2008 Aug;212(2):468-81
18579133
Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
4110397
J Neurosci. 2006 Nov 29;26(48):12447-55
17135406
Brain. 1999 May;122 ( Pt 5):817-25
10355668
Brain. 2006 Apr;129(Pt 4):911-22
16446281