title: Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.
abstract: Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY, USA.
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Hill
authors.affiliation: 1] Center for Regenerative Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [2] Harvard Stem Cell Institute, Boston, MA, USA [3] Harvard Medical School, Boston, MA, USA.
authors.forename: Amar
authors.initials: A
authors.lastname: Sahay
authors.affiliation: 1] Department of Neuroscience, Columbia University, New York, NY, USA [2] Department of Psychiatry, Columbia University, New York, NY, USA [3] Department of Pharmacology, Columbia University, New York, NY, USA [4] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000473:pathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D051028:bcl-2-Associated X Protein; D013629:Tamoxifen; D001973:Bromodeoxyuridine; D003345:Corticosterone
references.citation: Mol Psychiatry. 2015 Apr;20(4):500-8
references.pmid: 24751964
references.citation: Cell Tissue Res. 2013 Oct;354(1):203-19
references.pmid: 23595256
references.citation: J Neurosci. 2005 Sep 21;25(38):8680-5
references.pmid: 16177036
references.citation: Science. 2005 Oct 28;310(5748):679-83
references.pmid: 16254185
references.citation: Nat Neurosci. 2007 Mar;10(3):355-62
references.pmid: 17277773
references.citation: Nat Neurosci. 2007 Jun;10(6):727-34
references.pmid: 17486101
references.citation: Behav Brain Res. 2008 Nov 3;193(1):140-3
references.pmid: 18565601
references.citation: Neuroreport. 2009 Apr 22;20(6):553-7
references.pmid: 19322118
references.citation: Neuropsychopharmacology. 2009 May;34(6):1363-80
references.pmid: 18536703
references.citation: Neuron. 2009 May 28;62(4):479-93
references.pmid: 19477151
references.citation: Neuropsychopharmacology. 2009 Oct;34(11):2376-89
references.pmid: 19606083
references.citation: J Neurosci. 2000 Dec 15;20(24):9104-10
references.pmid: 11124987
references.citation: Neuropsychopharmacology. 2001 Dec;25(6):836-44
references.pmid: 11750177
references.citation: J Comp Neurol. 2003 Jun 9;460(4):563-72
references.pmid: 12717714
references.citation: Science. 2003 Aug 8;301(5634):805-9
references.pmid: 12907793
references.citation: J Comp Neurol. 2003 Dec 1;467(1):1-10
references.pmid: 14574675
references.citation: Neuropsychopharmacology. 2004 Jul;29(7):1321-30
references.pmid: 15085085
references.citation: J Comp Neurol. 1992 Oct 8;324(2):180-94
references.pmid: 1430328
references.citation: Brain Res. 1992 Oct 2;592(1-2):228-38
references.pmid: 1333341
references.citation: J Comp Neurol. 1993 Jun 1;332(1):1-20
references.pmid: 7685778
references.citation: Brain Res Bull. 1994;35(3):221-31
references.pmid: 7812801
references.citation: J Neurosci. 1997 Apr 1;17(7):2492-8
references.pmid: 9065509
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: Neuroscience. 2013 Nov 12;252:234-52
references.pmid: 23973415
references.citation: J Comp Neurol. 2014 Apr 1;522(5):1191-208
references.pmid: 24519019
references.citation: J Comp Neurol. 2014 Jun 1;522(8):1966-85
references.pmid: 24288185
references.citation: Neuropsychopharmacology. 2014 Jul;39(8):1861-71
references.pmid: 24518288
references.citation: Hippocampus. 2014 Jul;24(7):751-61
references.pmid: 24550158
references.citation: Cell. 2014 Sep 11;158(6):1324-34
references.pmid: 25215490
references.citation: Cell Rep. 2014 Sep 25;8(6):1731-40
references.pmid: 25220467
references.citation: Mol Psychiatry. 2014 Dec;19(12):1275-83
references.pmid: 24514565
references.citation: J Neurosci. 2010 Jan 13;30(2):723-30
references.pmid: 20071537
references.citation: Exp Neurol. 2005 Apr;192(2):251-64
references.pmid: 15755543
references.citation: Behav Brain Res. 2011 Jan 1;216(1):100-8
references.pmid: 20654656
references.citation: Mol Psychiatry. 2010 Dec;15(12):1152-63
references.pmid: 20308988
references.citation: Eur J Neurosci. 2011 Mar;33(6):1037-44
references.pmid: 21395846
references.citation: Nature. 2011 Apr 28;472(7344):466-70
references.pmid: 21460835
references.citation: Neuron. 2011 May 26;70(4):758-72
references.pmid: 21609830
references.citation: Neuron. 2011 Jun 9;70(5):908-23
references.pmid: 21658584
references.citation: Nature. 2011 Aug 25;476(7361):458-61
references.pmid: 21814201
references.citation: Mol Psychiatry. 2011 Dec;16(12):1177-88
references.pmid: 21537331
references.citation: J Neurosci. 2012 Mar 7;32(10):3529-39
references.pmid: 22399775
references.citation: Hippocampus. 2012 May;22(5):1188-201
references.pmid: 21739523
references.citation: J Comp Neurol. 2012 Sep 1;520(13):2805-23
references.pmid: 22605579
references.citation: Int J Dev Neurosci. 2012 Dec;30(8):615-21
references.pmid: 22867732
references.citation: J Neurosci. 2013 Feb 13;33(7):2961-72
references.pmid: 23407954
references.citation: Neuron. 2013 Mar 6;77(5):955-68
references.pmid: 23473324
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11272-7
references.pmid: 16055554