title: Neurogenesis and increase in differentiated neural cell survival via phosphorylation of Akt1 after fluoxetine treatment of stem cells.
abstract: Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μ M of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.
authors.affiliation: Stem Cell and Tissue Engineering Department, Research Center for Science and Technology in Medicine (RCSTiM), Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Anahita
authors.initials: A
authors.lastname: Rahmani
authors.forename: Danial
authors.initials: D
authors.lastname: Kheradmand
authors.forename: Peyman
authors.initials: P
authors.lastname: Keyhanvar
authors.forename: Alireza
authors.initials: A
authors.lastname: Shoae-Hassani
authors.forename: Amir
authors.initials: A
authors.lastname: Darbandi-Azar
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D044968:Regenerative Medicine; D012701:Serotonin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005473:Fluoxetine; D012701:Serotonin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
references.citation: Arch Immunol Ther Exp (Warsz). 2013 Feb;61(1):75-83
references.pmid: 23224340
references.citation: J Mol Neurosci. 2004;24(2):207-16
references.pmid: 15456934
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3392-7
references.pmid: 18305158
references.citation: J Neurosci. 2001 Aug 15;21(16):5871-84
references.pmid: 11487610
references.citation: J Neurosci. 1995 Oct;15(10):6975-85
references.pmid: 7472454
references.citation: J Biol Chem. 1997 Jul 25;272(30):18702-8
references.pmid: 9228041
references.citation: Oncogene. 2003 Dec 8;22(56):8983-98
references.pmid: 14663477
references.citation: Cell Biol Int. 2012 Oct 1;36(10):961-6
references.pmid: 22804708
references.citation: Am J Psychiatry. 2006 Nov;163(11):1905-17
references.pmid: 17074942
references.citation: Science. 2007 Jan 19;315(5810):336-8
references.pmid: 17234934
references.citation: Curr Opin Neurobiol. 2001 Jun;11(3):297-305
references.pmid: 11399427
references.citation: Neurosci Lett. 2006 Apr 24;397(3):185-9
references.pmid: 16413968
references.citation: J Neurochem. 2005 Jun;93(6):1551-60
references.pmid: 15935071
references.citation: Neurosci Lett. 2002 Aug 16;328(3):261-4
references.pmid: 12147321
references.citation: Nat Rev Neurosci. 2006 Mar;7(3):179-93
references.pmid: 16495940
references.citation: Cell Biol Int. 2011 Oct;35(10):1037-41
references.pmid: 21355850
references.citation: J Clin Invest. 2011 Jun;121(6):2326-35
references.pmid: 21576821
references.citation: J Neurosci Res. 2012 Mar;90(3):632-40
references.pmid: 22006722
references.citation: Mol Cell. 1999 Aug;4(2):143-52
references.pmid: 10488330
references.citation: CNS Neurol Disord Drug Targets. 2008 Apr;7(2):187-210
references.pmid: 18537646
references.citation: PLoS One. 2009 Jul 08;4(7):e6168
references.pmid: 19584922
references.citation: Mol Cell Biol. 1999 Aug;19(8):5800-10
references.pmid: 10409766
references.citation: Eur J Cell Biol. 2006 Nov;85(11):1189-99
references.pmid: 16860436
references.citation: J Biol Chem. 2003 Apr 18;278(16):13995-4001
references.pmid: 12584189
references.citation: Med Hypotheses. 2011 Jun;76(6):843-6
references.pmid: 21402451
references.citation: Science. 1997 Jan 31;275(5300):661-5
references.pmid: 9005851
references.citation: Neuroscience. 1994 Jul;61(2):203-9
references.pmid: 7969902
references.citation: Hum Reprod Update. 2007 Jan-Feb;13(1):87-101
references.pmid: 16960017
references.citation: PLoS Med. 2008 Jun 10;5(6):e117
references.pmid: 18593214
references.citation: Biochem Soc Trans. 2006 Dec;34(Pt 6):1287-90
references.pmid: 17073803
references.citation: J Tissue Eng Regen Med. 2015 Nov;9(11):1268-76
references.pmid: 23319462