title: Morphine Inhibited the Rat Neural Stem Cell Proliferation Rate by Increasing Neuro Steroid Genesis.
abstract: Up to present, a large number of reports unveiled exacerbating effects of both long- and short-term administration of morphine, as a potent analgesic agent, on opium-addicted individuals and a plethora of cell kinetics, although contradictory effect of morphine on different cells have been introduced until yet. To address the potent modulatory effect of morphine on neural multipotent precursors with emphasis on endogenous sex-related neurosteroids biosynthesis, we primed the rat neural stem cells isolated from embryonic rat telencephalon to various concentrations of morphine including 10, 20, 50 and 100 µM alone or in combination with naloxone (100 µM) over period of 72 h. Flow cytometric Ki-67 expression and Annexin-V/PI based necrosis and apoptosis of exposed cells were evaluated. The total content of dihydrotestosterone and estradiol in cell supernatant was measured by ELISA. According on obtained data, both concentration- and time-dependent decrement of cell viability were orchestrated thorough down-regulation of ki-67 and simultaneous up-regulation of Annexin-V. On the other hand, the addition of naloxone (100 µM), as Mu opiate receptor antagonist, could blunt the morphine-induced adverse effects. It also well established that time-course exposure of rat neural stem cells with morphine potently could accelerate the endogenous dihydrotestosterone and estradiol biosynthesis. Interestingly, naloxone could consequently attenuate the enhanced neurosteroidogenesis time-dependently. It seems that our results discover a biochemical linkage between an accelerated synthesis of sex-related steroids and rat neural stem cells viability.
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.|Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Feizy
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. alinour65@gmail.com.|Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. alinour65@gmail.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nourazarian
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hojjatollah
authors.initials: H
authors.lastname: Nozad Charoudeh
authors.affiliation: Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Abdyazdani
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Montazersaheb
authors.affiliation: Department of Medical Education, Medical Education Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohamadreza
authors.initials: M
authors.lastname: Narimani
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018377:Neurotransmitter Agents; D009020:Morphine
keywords: Cell viability; Morphine; Neurosteroids biosynthesis; Rat neural stem cell
references.citation: J Neurosci. 2003 Jan 1;23(1):240-51
references.pmid: 12514221
references.citation: Anesth Analg. 2007 Dec;105(6):1729-35, table of contents
references.pmid: 18042875
references.citation: Life Sci. 2015 Mar 1;124:128-35
references.pmid: 25623851
references.citation: Behav Neurosci. 2013 Jun;127(3):400-14
references.pmid: 23506438
references.citation: ScientificWorldJournal. 2007 Nov 02;7:98-111
references.pmid: 17982582
references.citation: Development. 1998 Jun;125(12):2251-61
references.pmid: 9584124
references.citation: Med Hypotheses. 2011 Jan;76(1):11-3
references.pmid: 20851532
references.citation: Med Hypotheses. 2011 Feb;76(2):225-9
references.pmid: 21051157
references.citation: Cancer Res. 2002 Aug 1;62(15):4491-8
references.pmid: 12154060
references.citation: Endocr Rev. 2010 Feb;31(1):98-132
references.pmid: 19903933
references.citation: Br J Pharmacol. 2001 Nov;134(6):1263-70
references.pmid: 11704646
references.citation: Anesthesiology. 2011 Dec;115(6):1363-81
references.pmid: 22020140
references.citation: Hippocampus. 2006;16(3):225-32
references.pmid: 16411182
references.citation: Anesthesiology. 1997 Nov;87(5):1075-81
references.pmid: 9366459
references.citation: PLoS One. 2014 Jul 29;9(7):e103043
references.pmid: 25072277
references.citation: Dev Neurobiol. 2007 Sep 1;67(10):1321-33
references.pmid: 17638384
references.citation: J Neurochem. 1996 May;66(5):1836-44
references.pmid: 8780008
references.citation: Stem Cells Dev. 2013 Mar 15;22(6):855-65
references.pmid: 23072248
references.citation: Brain Res. 2009 Jun 1;1273:138-43
references.pmid: 19344697
references.citation: Neurosci Lett. 1996 Jul 5;212(1):13-6
references.pmid: 8823751
references.citation: Baillieres Clin Gastroenterol. 1988 Jan;2(1):123-39
references.pmid: 2838107
references.citation: Mol Brain. 2011 Jul 30;4:31
references.pmid: 21801430
references.citation: Adv Pharm Bull. 2015 Nov;5(4):515-21
references.pmid: 26819924
references.citation: Cancer Res. 2003 Apr 15;63(8):1846-52
references.pmid: 12702572
references.citation: Neuroendocrinology. 1987 Aug;46(2):167-75
references.pmid: 3627377
references.citation: BMC Neurosci. 2010 Mar 09;11:33
references.pmid: 20214800
references.citation: J Pain. 2012 May;13(5):498-506
references.pmid: 22520687
references.citation: Neuroscience. 2008 Nov 11;157(1):70-9
references.pmid: 18832014
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5807-11
references.pmid: 9576966
references.citation: Endocrinology. 2002 Aug;143(8):2930-5
references.pmid: 12130558
references.citation: Stem Cells Dev. 2013 Mar 15;22(6):913-27
references.pmid: 23199293
references.citation: J Vis Exp. 2011 Aug 22;(54):null
references.pmid: 21876529
references.citation: Neuro Endocrinol Lett. 2009;30(2):195-203
references.pmid: 19675526
references.citation: Am J Cardiol. 2003 Oct 15;92(8):995-7
references.pmid: 14556883
references.citation: Cytometry A. 2009 Jan;75(1):14-24
references.pmid: 19023891
references.citation: J Clin Endocrinol Metab. 2000 Jun;85(6):2215-22
references.pmid: 10852454
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1876-81
references.pmid: 20133835
references.citation: J Neurosci. 2002 Sep 1;22(17):7650-61
references.pmid: 12196588
references.citation: J Clin Oncol. 2001 May 1;19(9):2542-54
references.pmid: 11331334
references.citation: Neurol Sci. 2013 Jan;34(1):19-23
references.pmid: 22258359
references.citation: Clin Interv Aging. 2008;3(2):273-8
references.pmid: 18686750
references.citation: BMC Biol. 2009 Jun 17;7:31
references.pmid: 19534760
references.citation: Blood. 2010 Jan 21;115(3):510-8
references.pmid: 19965654
references.citation: J Neurochem. 1996 Jul;67(1):413-22
references.pmid: 8667021
references.citation: Brain Res. 2009 Nov 17;1298:1-12
references.pmid: 19729001
references.citation: J Biol Chem. 2006 Sep 1;281(35):25492-501
references.pmid: 16803879
references.citation: J Neuroinflammation. 2012 Feb 16;9:32
references.pmid: 22340895
references.citation: Arch Iran Med. 2008 Nov;11(6):639-48
references.pmid: 18976035
references.citation: J Steroid Biochem. 1986 Jul;25(1):165-9
references.pmid: 2943941
references.citation: Nature. 1996 Oct 31;383(6603):819-23
references.pmid: 8893006
references.citation: Stem Cells. 2007 Jul;25(7):1645-53
references.pmid: 17412894
references.citation: Neuroscience. 2005;135(1):247-61
references.pmid: 16084657
references.citation: J Neurosci. 2011 Nov 9;31(45):16227-40
references.pmid: 22072674