title: Differential regulation of the variations induced by environmental richness in adult neurogenesis as a function of time: a dual birthdating analysis.
abstract: Adult hippocampal neurogenesis (AHN) augments after environmental enrichment (EE) and it has been related to some of the anxiolytic, antidepressant and neuroprotective effects of EE. Indeed, it has been suggested that EE specifically modulates hippocampal neurogenic cell populations over the course of time. Here we have used dual-birthdating to study two subpopulations of newborn neuron in mice (Mus musculus): those born at the beginning and at the end of enrichment. In this way, we demonstrate that while short-term cell survival is upregulated after an initial 1 week period of enrichment in 2 month old female mice, after long-term enrichment (2 months) neither cell proliferation nor the survival of the younger newly born cell populations are distinguishable from that observed in non-enriched control mice. In addition, we show that the survival of older newborn neurons alone (i.e. those born at the beginning of the enrichment) is higher than in controls, due to the significantly lower levels of cell death. Indeed, these parameters are rapidly adjusted to the sudden cessation of the EE conditions. These findings suggest both an early selective, long-lasting effect of EE on the neurons born in the initial stages of enrichment, and a quick response when the environment again becomes impoverished. Therefore, EE induces differential effects on distinct subpopulations of newborn neurons depending on the age of the immature cells and on the duration of the EE itself. The interaction of these two parameters constitutes a new, specific regulation of these neurogenic populations that might account for the long-term enrichment's behavioral effects.
authors.affiliation: Centro de Investigación en Red en Enfermedades Neurodegenerativas, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Llorens-Martín
authors.forename: Gonzalo S
authors.initials: GS
authors.lastname: Tejeda
authors.forename: José L
authors.initials: JL
authors.lastname: Trejo
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology; D007065:Idoxuridine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
chemical_list: C012244:5-chloro-2'-deoxyuridine; D007065:Idoxuridine; D003857:Deoxyuridine
references.citation: Nat Rev Neurosci. 2010 May;11(5):339-50
references.pmid: 20354534
references.citation: BMC Neurosci. 2006 Nov 15;7:77
references.pmid: 17105671
references.citation: Mol Psychiatry. 2007 Dec;12(12):1118-28
references.pmid: 17848918
references.citation: Mol Cell Neurosci. 2008 Feb;37(2):402-11
references.pmid: 18086533
references.citation: Development. 2003 Jan;130(2):391-9
references.pmid: 12466205
references.citation: Nat Neurosci. 2007 Sep;10(9):1110-5
references.pmid: 17726477
references.citation: Nature. 1997 Apr 3;386(6624):493-5
references.pmid: 9087407
references.citation: J Neurosci. 1998 May 1;18(9):3206-12
references.pmid: 9547229
references.citation: Neuroscience. 2007 Jul 13;147(3):631-8
references.pmid: 17570601
references.citation: Cereb Cortex. 2003 Aug;13(8):845-51
references.pmid: 12853371
references.citation: Eur J Neurosci. 2006 Apr;23(7):1829-38
references.pmid: 16623840
references.citation: Nat Neurosci. 2008 Oct;11(10):1153-61
references.pmid: 18758458
references.citation: Ageing Res Rev. 2006 Aug;5(3):354-69
references.pmid: 16949888
references.citation: ILAR J. 2005;46(2):148-61
references.pmid: 15775024
references.citation: Cell. 2005 Mar 11;120(5):701-13
references.pmid: 15766532
references.citation: Nat Neurosci. 1999 Mar;2(3):266-70
references.pmid: 10195220
references.citation: Neuroscience. 1993 Sep;56(2):337-44
references.pmid: 8247264
references.citation: Brain Res. 2004 Aug 13;1017(1-2):21-31
references.pmid: 15261095
references.citation: Nat Neurosci. 2006 Jun;9(6):729-31
references.pmid: 16648847
references.citation: Neuron. 2008 Aug 28;59(4):568-80
references.pmid: 18760694
references.citation: J Neurosci. 2008 Nov 12;28(46):11785-91
references.pmid: 19005040
references.citation: Eur J Neurosci. 2003 May;17(10):2042-6
references.pmid: 12786970
references.citation: J Comp Neurol. 2008 Aug 1;509(4):372-81
references.pmid: 18512685
references.citation: Curr Top Dev Biol. 2009;87:149-74
references.pmid: 19427519
references.citation: Neurosci Biobehav Rev. 2009 Mar;33(3):232-52
references.pmid: 18786562
references.citation: Neuroscientist. 2009 Apr;15(2):134-48
references.pmid: 19307421
references.citation: Nature. 2008 Feb 21;451(7181):1004-7
references.pmid: 18235445
references.citation: Biol Psychiatry. 2006 Dec 15;60(12):1314-23
references.pmid: 16806094
references.citation: Cell. 2009 Nov 13;139(4):814-27
references.pmid: 19914173
references.citation: Behav Brain Res. 2002 Aug 21;134(1-2):185-200
references.pmid: 12191805
references.citation: Eur J Neurosci. 2005 Jan;21(2):513-21
references.pmid: 15673450
references.citation: Nat Med. 1999 Apr;5(4):448-53
references.pmid: 10202938
references.citation: J Microsc. 1988 Apr;150(Pt 1):1-20
references.pmid: 3043005
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31
references.pmid: 10557337
references.citation: J Comp Neurol. 2009 Nov 10;517(2):123-33
references.pmid: 19731267
references.citation: J Neurosci. 2007 Mar 21;27(12):3252-9
references.pmid: 17376985
references.citation: Hippocampus. 2006;16(3):250-60
references.pmid: 16411242
references.citation: Behav Pharmacol. 2007 Sep;18(5-6):391-418
references.pmid: 17762509
references.citation: Neuromolecular Med. 2008;10(2):59-66
references.pmid: 18286387
references.citation: Curr Opin Psychiatry. 2008 May;21(3):290-5
references.pmid: 18382230
references.citation: PLoS Biol. 2007 Aug;5(8):e214
references.pmid: 17683201
references.citation: Brain Res. 2009 Feb 23;1256:173-9
references.pmid: 19135431
references.citation: Genes Brain Behav. 2002 Jan;1(1):46-54
references.pmid: 12886949
references.citation: Trends Neurosci. 2004 Aug;27(8):447-52
references.pmid: 15271491
references.citation: Hippocampus. 2006;16(5):480-90
references.pmid: 16596582
references.citation: Hippocampus. 2009 Oct;19(10):1008-18
references.pmid: 19219917
references.citation: Neurobiol Learn Mem. 2008 Oct;90(3):511-8
references.pmid: 18675926
references.citation: Neuron. 2001 Dec 6;32(5):911-26
references.pmid: 11738035
references.citation: Nat Neurosci. 2006 Jun;9(6):723-7
references.pmid: 16732202
references.citation: Mol Cell Neurosci. 2010 Jun;44(2):109-17
references.pmid: 20206269
references.citation: Nat Rev Neurosci. 2006 Sep;7(9):697-709
references.pmid: 16924259
references.citation: Ann Neurol. 2002 Aug;52(2):135-43
references.pmid: 12210782
references.citation: Eur J Neurosci. 2006 Oct;24(7):1850-6
references.pmid: 17040481
references.citation: Exp Neurol. 2009 Mar;216(1):184-92
references.pmid: 19118549
references.citation: PLoS One. 2008 Apr 09;3(4):e1959
references.pmid: 18509506
references.citation: J Physiol. 2008 Aug 15;586(16):3759-65
references.pmid: 18499723
references.citation: Rev Neurosci. 2007;18(2):93-114
references.pmid: 17593874
references.citation: Neurosci Biobehav Rev. 2008;32(4):657-74
references.pmid: 18178250
references.citation: Physiol Behav. 2001 Jul;73(4):649-58
references.pmid: 11495671
references.citation: Neuroscience. 2008 Jun 23;154(2):521-9
references.pmid: 18502050