Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus.
aging
dentate gyrus
doublecortin
human hippocampus
neural progenitors
neurogenesis
new neurons
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
24 03 2021
24 03 2021
Historique:
received:
26
05
2020
revised:
06
11
2020
accepted:
10
11
2020
entrez:
25
3
2021
pubmed:
26
3
2021
medline:
18
8
2021
Statut:
ppublish
Résumé
Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interpreted as evidence for high rates of adult neurogenesis, even at older ages. However, most of these DCX-labeled cells have mature morphology. Furthermore, studies in the adult human DG have not found a germinal region containing dividing progenitor cells. In this Dual Perspectives article, we show that dual antigen retrieval is not required for the detection of DCX in multiple human brain regions of infants or adults. We review prior studies and present new data showing that DCX is not uniquely expressed by newly born neurons: DCX is present in adult amygdala, entorhinal and parahippocampal cortex neurons despite being absent in the neighboring DG. Analysis of available RNA-sequencing datasets supports the view that DG neurogenesis is rare or absent in the adult human brain. To resolve the conflicting interpretations in humans, it is necessary to identify and visualize dividing neuronal precursors or develop new methods to evaluate the age of a neuron at the single-cell level.
Identifiants
pubmed: 33762407
pii: 41/12/2554
doi: 10.1523/JNEUROSCI.0676-20.2020
pmc: PMC8018729
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2554-2565Subventions
Organisme : NINDS NIH HHS
ID : P01 NS083513
Pays : United States
Organisme : NINDS NIH HHS
ID : DP2 NS122550
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH123156
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113896
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS091537
Pays : United States
Informations de copyright
Copyright © 2021 the authors.
Références
Neurosci Lett. 2004 Oct 7;369(1):24-7
pubmed: 15380301
J Neuroinflammation. 2017 Mar 3;14(1):45
pubmed: 28253906
Sci Rep. 2019 Dec 3;9(1):18194
pubmed: 31796832
Cent Nerv Syst Agents Med Chem. 2010 Mar;10(1):32-46
pubmed: 20236041
PLoS One. 2011;6(10):e25760
pubmed: 22022443
Brain. 2007 Dec;130(Pt 12):3321-35
pubmed: 18055496
PLoS One. 2008 Feb 20;3(2):e1631
pubmed: 18286188
Med Oral Patol Oral Cir Bucal. 2013 Mar 01;18(2):e174-9
pubmed: 23229269
Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9484-9
pubmed: 26170290
Elife. 2020 Jul 21;9:
pubmed: 32690132
Front Neurosci. 2017 Mar 28;11:143
pubmed: 28400715
J Neurosci. 2014 Sep 3;34(36):11929-47
pubmed: 25186741
Science. 2015 Mar 6;347(6226):1138-42
pubmed: 25700174
J Comp Neurol. 2011 Mar 1;519(4):690-713
pubmed: 21246550
Biotechniques. 2010 Mar;48(3):197-209
pubmed: 20359301
Cereb Cortex. 2020 Mar 14;30(3):1499-1515
pubmed: 31647533
Nat Neurosci. 2003 May;6(5):507-18
pubmed: 12704391
Eur J Neurosci. 2003 Jan;17(2):205-11
pubmed: 12542656
Cereb Cortex. 2018 Jul 1;28(7):2610-2621
pubmed: 29688272
Eur J Neurosci. 2005 Oct;22(8):1928-41
pubmed: 16262632
Brain Res. 2004 Aug 13;1017(1-2):21-31
pubmed: 15261095
Science. 1994 May 20;264(5162):1145-8
pubmed: 8178174
Stem Cell Res. 2017 Mar;19:82-93
pubmed: 28088038
Cell. 2011 Apr 29;145(3):423-34
pubmed: 21496894
Mol Cell Neurosci. 2003 Nov;24(3):603-13
pubmed: 14664811
BMC Neurosci. 2012 Jun 14;13:64
pubmed: 22697290
Nat Protoc. 2020 Feb;15(2):668-693
pubmed: 31915385
Neurosci Lett. 2013 Aug 26;548:244-8
pubmed: 23721782
Cell Cycle. 2007 Feb 1;6(3):318-29
pubmed: 17297309
J Neurosci. 1997 Jul 1;17(13):5046-61
pubmed: 9185542
J Comp Neurol. 1965 Jun;124(3):319-35
pubmed: 5861717
PLoS One. 2014 Jun 05;9(6):e99253
pubmed: 24901457
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1446-51
pubmed: 23302686
J Comp Neurol. 2003 Dec 1;467(1):1-10
pubmed: 14574675
Nat Neurosci. 2003 Dec;6(12):1277-83
pubmed: 14625554
Dev Neurobiol. 2019 Mar;79(3):268-280
pubmed: 30916471
J Comp Neurol. 2004 Oct 25;478(4):359-78
pubmed: 15384070
Science. 2007 Oct 19;318(5849):393; author reply 393
pubmed: 17947566
Front Neurosci. 2018 Jul 20;12:497
pubmed: 30079011
J Chem Neuroanat. 2007 Jul;33(4):202-9
pubmed: 17467233
Neural Regen Res. 2020 Jul;15(7):1290-1299
pubmed: 31960815
Eur J Neurosci. 2013 Jan;37(1):10-22
pubmed: 23066968
Brain. 2010 Sep;133(9):2763-77
pubmed: 20576695
Brain Behav Evol. 2014;84(1):1-4
pubmed: 25034511
Science. 2009 Apr 3;324(5923):98-102
pubmed: 19342590
Science. 1985 Mar 1;227(4690):1054-6
pubmed: 3975601
Eur J Neurosci. 2011 Sep;34(6):884-907
pubmed: 21929623
Cell Stem Cell. 2018 Apr 5;22(4):589-599.e5
pubmed: 29625071
Neuropathol Appl Neurobiol. 2016 Dec;42(7):621-638
pubmed: 27424496
J Comp Neurol. 2014 Apr 15;522(6):1299-315
pubmed: 24115109
Epilepsia. 2002;43 Suppl 5:68-73
pubmed: 12121298
Trends Neurosci. 2019 Mar;42(3):164-178
pubmed: 30686490
J Neurosci. 2014 Aug 13;34(33):10906-23
pubmed: 25122892
J Cell Biochem. 2017 Oct;118(10):3111-3118
pubmed: 28374892
J Comp Neurol. 2016 Feb 15;524(3):646-64
pubmed: 26417888
Sci Rep. 2011;1:28
pubmed: 22355547
Nat Commun. 2019 Jun 21;10(1):2748
pubmed: 31227709
Trends Genet. 2013 Oct;29(10):569-74
pubmed: 23810203
FEBS Lett. 2009 Dec 17;583(24):3966-73
pubmed: 19850042
Front Neuroanat. 2009 Oct 13;3:17
pubmed: 19862344
Front Neurosci. 2020 Feb 04;14:75
pubmed: 32116519
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Mol Brain. 2019 Dec 10;12(1):108
pubmed: 31823803
Front Neurosci. 2018 Oct 05;12:706
pubmed: 30344473
Brain Struct Funct. 2015 Jan;220(1):361-83
pubmed: 24178679
Front Neurosci. 2011 Feb 15;5:17
pubmed: 21415912
Genome Biol. 2003;4(9):117
pubmed: 12952525
EMBO J. 2006 Oct 4;25(19):4448-57
pubmed: 16957770
Cell Stem Cell. 2007 Dec 13;1(6):612-27
pubmed: 18371403
Alzheimers Dement. 2018 Aug;14(8):1022-1037
pubmed: 29630865
Aging (Albany NY). 2009 Apr;1(4):382-8
pubmed: 19946466
J Neurosci. 2018 Jan 24;38(4):826-842
pubmed: 29217680
Front Neurosci. 2017 Oct 23;11:570
pubmed: 29109674
Cereb Cortex. 2018 Jul 1;28(7):2458-2478
pubmed: 29722804
Nature. 2011 Sep 28;478(7369):382-6
pubmed: 21964341
Nat Methods. 2017 Oct;14(10):955-958
pubmed: 28846088
Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10326-31
pubmed: 21646517
Nat Neurosci. 2018 Sep;21(9):1171-1184
pubmed: 30154505
Ann Neurol. 2016 Dec;80(6):797-810
pubmed: 27862206
PLoS One. 2010 Jan 29;5(1):e8809
pubmed: 20126454
Cell. 2013 Jun 6;153(6):1219-1227
pubmed: 23746839
Science. 1977 Sep 9;197(4308):1092-4
pubmed: 887941
J Comp Neurol. 1969 Dec;137(4):433-57
pubmed: 5361244
Angew Chem Int Ed Engl. 2010 Jul 19;49(31):5375-7
pubmed: 20583021
Biopreserv Biobank. 2015 Oct;13(5):311-9
pubmed: 26484571
Neuroscience. 2011 May 5;181:18-27
pubmed: 21382447
Nat Med. 2019 Apr;25(4):554-560
pubmed: 30911133
Neurosci Lett. 2001 Sep 14;310(2-3):173-7
pubmed: 11585595
Cereb Cortex. 2016 May;26(5):2191-2204
pubmed: 25824535
Cereb Cortex. 2020 Jun 1;30(7):4092-4109
pubmed: 32108222
J Neurosci. 1999 Dec 1;19(23):10228-36
pubmed: 10575020
Nat Med. 1998 Nov;4(11):1313-7
pubmed: 9809557
Nature. 2002 Feb 28;415(6875):1030-4
pubmed: 11875571
Nature. 2018 Mar 15;555(7696):377-381
pubmed: 29513649
Science. 2007 Mar 2;315(5816):1243-9
pubmed: 17303719
J Comp Neurol. 2013 Jan 1;521(1):169-88
pubmed: 22700217
J Neurosci. 2001 Sep 15;21(18):7153-60
pubmed: 11549726
Acta Neuropathol Commun. 2018 Jul 13;6(1):60
pubmed: 30005693
Cell Stem Cell. 2018 Dec 6;23(6):780-781
pubmed: 30526879
J Neurosci. 1996 May 15;16(10):3397-411
pubmed: 8627375
J Neurosci. 2002 Feb 1;22(3):624-8
pubmed: 11826090
BMC Genomics. 2006 Jul 26;7:188
pubmed: 16869982
Neurosci Lett. 2009 Oct 16;464(1):14-7
pubmed: 19682546
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5768-73
pubmed: 10318959
J Neurosci. 2006 Jan 4;26(1):3-11
pubmed: 16399667
Cell. 2014 Feb 27;156(5):1072-83
pubmed: 24561062
Mol Brain. 2019 Aug 5;12(1):69
pubmed: 31383032
J Cell Biol. 1981 Aug;90(2):435-47
pubmed: 7026573
Microsc Res Tech. 1999 Jun 15;45(6):353-8
pubmed: 10402263
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13036-41
pubmed: 14559968
J Neurosci. 2002 Jul 15;22(14):6106-13
pubmed: 12122071
Neuron. 1999 Jun;23(2):257-71
pubmed: 10399933