title: Serotonin is required for exercise-induced adult hippocampal neurogenesis.
abstract: Voluntary wheel running has long been known to induce precursor cell proliferation in adult hippocampal neurogenesis in rodents. However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase (TPH) 2 deficient (Tph2-deficient) mice that lack brain serotonin, we explored the relationship between serotonin signaling and exercise-induced neurogenesis. Surprisingly, Tph2-deficient mice exhibit normal baseline hippocampal neurogenesis but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central serotonin in young-adult and aged mice. Lack of brain serotonin further results in alterations at the stage of Sox2-positive precursor cells, suggesting physiological adaptations to changes in serotonin supply to maintain homeostasis in the neurogenic niche. We conclude that serotonin plays a direct and acute regulatory role in activity-dependent hippocampal neurogenesis. The understanding of exercise-induced neurogenesis might offer preventive but also therapeutic opportunities in depression and age-related cognitive decline.
authors: Max-Delbruck-Center for Molecular Medicine, 13125 Berlin, Germany. friederike.klempin@mdc-berlin.de
authors: Friederike
authors: F
authors: Klempin
authors: Daniel
authors: D
authors: Beis
authors: Valentina
authors: V
authors: Mosienko
authors: Gerd
authors: G
authors: Kempermann
authors: Michael
authors: M
authors: Bader
authors: Natalia
authors: N
authors: Alenina
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000172:deficiency
chemical_list: D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; D001973:Bromodeoxyuridine
references: Cereb Cortex. 2003 Aug;13(8):845-51
references: 12853371
references: Neuropsychopharmacology. 2003 Sep;28(9):1562-71
references: 12838272
references: Brain Res. 2006 Feb 23;1075(1):48-59
references: 16460708
references: Glia. 2006 Dec;54(8):805-14
references: 16958090
references: J Neurosci. 2000 Apr 15;20(8):2926-33
references: 10751445
references: Science. 2003 Jan 3;299(5603):76
references: 12511643
references: Cell Commun Signal. 2010 Jun 17;8:12
references: 20565726
references: Transl Psychiatry. 2012 May 29;2:e122
references: 22832966
references: Science. 2003 Aug 8;301(5634):805-9
references: 12907793
references: Neuroscience. 2008 Jun 23;154(2):521-9
references: 18502050
references: J Neurosci Res. 1999 Jan 1;55(1):54-70
references: 9890434
references: Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):13094-9
references: 22826223
references: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8233-8
references: 16702546
references: Brain Res. 1996 Nov 18;740(1-2):245-52
references: 8973821
references: J Neurosci. 2000 Dec 15;20(24):9104-10
references: 11124987
references: Neuropsychopharmacology. 1999 Nov;21(5):679-82
references: 10516964
references: Nat Neurosci. 1999 Mar;2(3):266-70
references: 10195220
references: J Pharmacol Exp Ther. 2001 Nov;299(2):401-7
references: 11602648
references: Neurobiol Aging. 2006 Oct;27(10):1505-13
references: 16271278
references: PLoS One. 2012;7(8):e43157
references: 22912815
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11946-50
references: 12181492
references: Eur J Neurosci. 2003 Nov;18(10):2803-12
references: 14656329
references: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31
references: 10557337
references: Hippocampus. 2000;10(1):37-46
references: 10706215
references: Neurobiol Aging. 2005 Apr;26(4):511-20
references: 15653179
references: J Comp Neurol. 2003 Dec 22;467(4):455-63
references: 14624480
references: Neurosci Lett. 2001 Mar 30;301(2):143-6
references: 11248443
references: Brain Res. 2010 Jun 23;1341:93-9
references: 20381469
references: Front Mol Neurosci. 2010 Jul 30;3:
references: 20721314
references: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10332-7
references: 19520831
references: Hippocampus. 2010 Apr;20(4):513-23
references: 19489006
references: Neuroscience. 2003;121(1):1-7
references: 12946694
references: J Neurosci. 2001 Mar 1;21(5):1628-34
references: 11222653
references: Hippocampus. 2009 Oct;19(10):889-97
references: 18958850
references: Nature. 2012 Sep 6;489(7414):150-4
references: 22842902
references: Acta Physiol Scand. 2002 Sep;176(1):65-9
references: 12193220