title: GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior.
abstract: Impaired GABA-mediated neurotransmission has been implicated in many neurologic diseases, including epilepsy, intellectual disability and psychiatric disorders. We found that inhibitory neuron transplantation into the hippocampus of adult mice with confirmed epilepsy at the time of grafting markedly reduced the occurrence of electrographic seizures and restored behavioral deficits in spatial learning, hyperactivity and the aggressive response to handling. In the recipient brain, GABA progenitors migrated up to 1,500 μm from the injection site, expressed genes and proteins characteristic for interneurons, differentiated into functional inhibitory neurons and received excitatory synaptic input. In contrast with hippocampus, cell grafts into basolateral amygdala rescued the hyperactivity deficit, but did not alter seizure activity or other abnormal behaviors. Our results highlight a critical role for interneurons in epilepsy and suggest that interneuron cell transplantation is a powerful approach to halting seizures and rescuing accompanying deficits in severely epileptic mice.
authors: Epilepsy Research Laboratory, University of California, San Francisco, California, USA. robert.huntiii@ucsf.edu
authors: Robert F
authors: RF
authors: Hunt
authors: Kelly M
authors: KM
authors: Girskis
authors: John L
authors: JL
authors: Rubenstein
authors: Arturo
authors: A
authors: Alvarez-Buylla
authors: Scott C
authors: SC
authors: Baraban
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D059330:GABAergic Neurons / Q000473:pathology / Q000637:transplantation*; D007395:Interneurons / Q000637:transplantation*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*; D013687:Telencephalon / Q000196:embryology / Q000473:pathology / Q000637:transplantation
references: Cell Transplant. 2010;19(5):549-64
references: 20144261
references: Prog Neurobiol. 1991;37(1):1-82
references: 1947175
references: Exp Neurol. 2007 Oct;207(2):329-49
references: 17714705
references: Exp Neurol. 2007 Jun;205(2):501-5
references: 17442304
references: Epilepsy Behav. 2005 Dec;7(4):629-38
references: 16246633
references: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15472-7
references: 19706400
references: J Neurosci. 2007 Mar 28;27(13):3383-7
references: 17392454
references: Brain Res Brain Res Rev. 2001 Aug;36(1):60-90
references: 11516773
references: PLoS One. 2012;7(7):e40555
references: 22792368
references: Nat Neurosci. 2001 Jan;4(1):52-62
references: 11135645
references: Cell. 2012 Apr 27;149(3):708-21
references: 22541439
references: Nature. 2012 Sep 20;489(7416):385-90
references: 22914087
references: Lancet Neurol. 2008 Feb;7(2):151-60
references: 18207113
references: J Neurophysiol. 1989 Apr;61(4):747-58
references: 2542471
references: Neurobiol Dis. 2010 Nov;40(2):478-89
references: 20682341
references: Neuroscience. 1991;42(2):351-63
references: 1716744
references: J Neurosci. 2006 Jul 12;26(28):7380-9
references: 16837585
references: Nature. 2012 Nov 1;491(7422):109-13
references: 23041929
references: Nat Commun. 2012;3:1060
references: 22968706
references: J Neurosci. 2004 Mar 17;24(11):2612-22
references: 15028753
references: J Comp Neurol. 2003 Dec 1;467(1):60-79
references: 14574680
references: Nat Neurosci. 1999 May;2(5):461-6
references: 10321251
references: Neuron. 2005 Nov 23;48(4):591-604
references: 16301176
references: Science. 2012 Aug 10;337(6095):735-7
references: 22879515
references: J Neurosci. 1999 Sep 15;19(18):7881-8
references: 10479690
references: J Neurosci. 2002 Jun 15;22(12):5204-9
references: 12077215
references: J Vis Exp. 2012 Jan 29;(59):e3638
references: 22314943
references: Nat Commun. 2013;4:1376
references: 23340416
references: Cereb Cortex. 2010 Oct;20(10):2333-47
references: 20083553
references: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references: 4110397
references: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14934-9
references: 8962159
references: J Neurosci. 2003 Mar 15;23(6):2440-52
references: 12657704
references: Nat Neurosci. 1999 Jun;2(6):499-500
references: 10448211
references: Epilepsy Res. 2002 Apr;49(2):109-20
references: 12049799
references: Brain Res. 2012 Apr 23;1450:125-37
references: 22405727
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9572-7
references: 12881482
references: Nat Neurosci. 2013 Jan;16(1):64-70
references: 23143518
references: J Neurosci. 2011 Jul 27;31(30):10948-70
references: 21795545
references: J Vis Exp. 2007;(7):262
references: 18989433