title: Hippocampal interneuron transplants reverse aberrant dopamine system function and behavior in a rodent model of schizophrenia.
abstract: Schizophrenia patients exhibit increased hippocampal activity that is correlated with positive symptoms. Although the cause of this hippocampal hyperactivity has not been demonstrated, it likely involves a decrease in GABAergic signaling. Thus, we posit that restoring GABAergic function may provide a novel therapeutic approach for the treatment of schizophrenia. It has been demonstrated that transplanted GABAergic precursor cells from the medial ganglionic eminence (MGE) can migrate and differentiate into mature interneurons. Here, we demonstrate that ventral hippocampal MGE transplants can restore hippocampal function and normalize downstream dopamine neuron activity in a rodent model of schizophrenia. Furthermore, MGE transplants also reverse the hyper-responsive locomotor response to amphetamine. Taken together, these data demonstrate that restoring interneuron function reverses neurophysiological and behavioral deficits in a rodent model of schizophrenia and moreover, demonstrate the feasibility of a neuronal transplant procedure as a potential novel therapeutic approach for the treatment of schizophrenia.
authors: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX, USA.
authors: S M
authors: SM
authors: Perez
authors: D J
authors: DJ
authors: Lodge
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000637:transplantation*; D008297:Male; D008473:Median Eminence / Q000166:cytology; D008746:Methylazoxymethanol Acetate; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012559:Schizophrenia / Q000139:chemically induced / Q000473:pathology* / Q000601:surgery*
chemical_list: D008746:Methylazoxymethanol Acetate; D000661:Amphetamine
references: J Neurosci. 2009 Feb 25;29(8):2344-54
references: 19244511
references: J Neurosci. 2006 Jul 12;26(28):7380-9
references: 16837585
references: Int J Neuropsychopharmacol. 2004 Mar;7 Suppl 1:S1-5
references: 14972078
references: PLoS One. 2012;7(1):e29754
references: 22238649
references: Nat Neurosci. 1999 May;2(5):461-6
references: 10321251
references: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2569-74
references: 9122236
references: Transl Psychiatry. 2013 Jan 15;3:e215
references: 23321812
references: Int J Neuropsychopharmacol. 2013 Jul;16(6):1331-9
references: 23190686
references: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15472-7
references: 19706400
references: J Neurosci. 2011 Feb 23;31(8):2843-54
references: 21414906
references: Neuropsychopharmacology. 2011 Aug;36(9):1903-11
references: 21562483
references: Exp Neurol. 1973 Nov;41(2):461-531
references: 4355646
references: Psychopharmacology (Berl). 2004 Jun;174(1):151-62
references: 15205886
references: Curr Psychiatry Rep. 2010 Aug;12(4):335-44
references: 20556669
references: J Neurosci. 2011 Oct 5;31(40):14116-25
references: 21976496
references: Neuroscience. 1983 Oct;10(2):301-15
references: 6633863
references: Biol Psychiatry. 2006 Aug 1;60(3):253-64
references: 16581031
references: Neurobiol Dis. 2013 Feb;50:179-86
references: 23103418
references: Lancet. 1979 Feb 3;1(8110):237-9
references: 84898
references: Behav Brain Res. 2009 Dec 7;204(2):306-12
references: 19716984
references: Arch Gen Psychiatry. 2009 Sep;66(9):938-46
references: 19736350
references: J Neurosci. 2003 Jul 16;23(15):6315-26
references: 12867516
references: Hippocampus. 2001;11(5):543-50
references: 11732707
references: Epilepsia. 2010 Jul;51 Suppl 3:66-70
references: 20618404
references: Brain Res Bull. 2001 May 1;55(1):71-7
references: 11427340
references: Nat Neurosci. 1998 Aug;1(4):318-23
references: 10195166
references: Trends Pharmacol Sci. 2011 Sep;32(9):507-13
references: 21700346
references: J Psychopharmacol. 1999 Dec;13(4):358-71
references: 10667612
references: Trends Neurosci. 2007 May;30(5):220-7
references: 17400299
references: Schizophr Res. 2009 Oct;114(1-3):110-8
references: 19683896
references: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references: 15803162
references: Neuropsychopharmacology. 2006 Jan;31(1):221-30
references: 16123774
references: J Neurosci. 2007 Oct 17;27(42):11424-30
references: 17942737
references: Cell Stem Cell. 2010 Mar 5;6(3):238-50
references: 20207227