title: Downregulation of serotonergic gene expression in the Raphe nuclei of the midbrain under chronic social defeat stress in male mice.
abstract: There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression, and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. The serotonergic genes were the Tph2, Sert, Maoa, and Htr1a. The Bdnf and Creb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf, and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. The expression of the serotonergic genes as well as the Creb gene is not restored to the control level after the 2 weeks of relative rest. mRNA levels of Bdnf gene are not recovered to the control levels, although some upregulation was observed in rested losers. CSDS experience inducing the development of mixed anxiety/depression-like state in male mice downregulates the expression of serotonergic genes associated with the synthesis, inactivation, and reception of serotonin. The Bdnf and Creb genes in the midbrain raphe nuclei are also downregulated under CSDS. Period of relative rest is not enough for most serotonergic genes to recover expression to the control levels.
authors: Institute of Chemical Biology and Basic Medicine SD RAS, pr. Ac. Lavrentjeva, 8, Novosibirsk, 630090, Russia.
authors: Ul'yana A
authors: UA
authors: Boyarskikh
authors: Natalya P
authors: NP
authors: Bondar
authors: Maxim L
authors: ML
authors: Filipenko
authors: Natalia N
authors: NN
authors: Kudryavtseva
mesh_terms: D000378:Agonistic Behavior; D000818:Animals; D015536:Down-Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012919:Social Behavior; D013315:Stress, Psychological / Q000235:genetics*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012701:Serotonin
references: Mol Endocrinol. 2001 Oct;15(10):1748-57
references: 11579207
references: Neurosci Lett. 2001 Jun 15;305(3):189-92
references: 11403937
references: Cell Mol Neurobiol. 2006 Mar;26(2):145-62
references: 16763781
references: Ann N Y Acad Sci. 2008 Dec;1148:86-94
references: 19120094
references: Depress Anxiety. 2000;12 Suppl 1:2-19
references: 11098410
references: CNS Spectr. 2006 Dec;11(12 Suppl 15):12-21
references: 17146414
references: Psychopharmacology (Berl). 2005 Jun;180(1):95-9
references: 15918078
references: Usp Fiziol Nauk. 2004 Oct-Dec;35(4):19-40
references: 15573884
references: Brain Res Mol Brain Res. 2003 Mar 17;111(1-2):182-8
references: 12654518
references: Dokl Akad Nauk. 1998 Nov;363(3):405-8
references: 9891212
references: Behav Brain Res. 2009 Feb 11;197(2):262-78
references: 18983874
references: BMC Mol Biol. 2009 Mar 03;10:17
references: 19257903
references: Neuron. 2002 Mar 28;34(1):13-25
references: 11931738
references: Eur Neuropsychopharmacol. 2007 May-Jun;17(6-7):417-29
references: 17182223
references: Biol Psychiatry. 2006 Jun 15;59(12):1144-50
references: 16457782
references: Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):290-2
references: 15857692
references: Stress. 2011 Sep;14(5):537-48
references: 21438787
references: Mol Psychiatry. 2007 Dec;12(12):1079-88
references: 17700574
references: Histol Histopathol. 2010 Feb;25(2):237-58
references: 20017110
references: Front Neuroendocrinol. 2004 Jul;25(2):77-107
references: 15571756
references: Ann Med. 2002;34(5):348-56
references: 12452479
references: Science. 2006 Feb 10;311(5762):864-8
references: 16469931
references: Lancet. 2003 Feb 22;361(9358):653-61
references: 12606176
references: Psychopharmacology (Berl). 2011 Feb;213(2-3):265-87
references: 21107537
references: Bipolar Disord. 2002 Jun;4(3):183-94
references: 12180273
references: BMC Med Genomics. 2010 Aug 03;3:32
references: 20682026
references: Dialogues Clin Neurosci. 2009;11(3):239-55
references: 19877493
references: Acta Pharmacol Sin. 2011 Jan;32(1):3-11
references: 21131999
references: Cell. 2007 Oct 19;131(2):391-404
references: 17956738
references: Psychiatry Clin Neurosci. 2010 Aug;64(4):341-57
references: 20653908
references: Pharmacol Ther. 2008 Nov;120(2):102-28
references: 18789966
references: Psychiatr Danub. 2012 Sep;24 Suppl 1:S169-71
references: 22945215
references: Can J Physiol Pharmacol. 1998 Mar;76(3):278-83
references: 9673791
references: J Neurosci. 2009 Oct 14;29(41):12764-7
references: 19828787
references: Stress. 2000 May;3(3):201-8
references: 10938581
references: PLoS One. 2010 Nov 23;5(11):e14089
references: 21124898
references: Bioessays. 2007 Oct;29(10):957-61
references: 17876779
references: Biochem Biophys Res Commun. 2010 Dec 17;403(3-4):385-90
references: 21081112
references: Pharmacol Biochem Behav. 1991 Feb;38(2):315-20
references: 2057501
references: Neurosci Behav Physiol. 2005 Nov;35(9):917-24
references: 16270173
references: Neuroscience. 2013 Jun 3;239:214-27
references: 22922121
references: Science. 2006 Jun 16;312(5780):1598-9; author reply 1598-9
references: 16778038
references: J Comp Physiol B. 2010 Apr;180(4):619-29
references: 20033416
references: Brain Res Mol Brain Res. 1996 May;38(1):71-6
references: 8737669
references: Health Technol Assess. 2007 Oct;11(39):iii-iv, ix-206
references: 17903393
references: Trends Neurosci. 2005 Aug;28(8):436-45
references: 15982754
references: Genetika. 2004 Jun;40(6):732-48
references: 15341265
references: Neuropsychopharmacology. 2008 Jan;33(1):73-83
references: 17882234
references: J Neurosci Res. 2009 Jan;87(1):34-41
references: 18711751
references: Neuropsychopharmacology. 2001 Aug;25(2):185-94
references: 11425502
references: Dev Neurobiol. 2010 Apr;70(5):289-97
references: 20186711
references: Neuroreport. 1999 Sep 29;10(14):3015-9
references: 10549815
references: Nat Neurosci. 2006 Apr;9(4):519-25
references: 16501568
references: Brain Res. 2004 Oct 29;1025(1-2):10-20
references: 15464739
references: BMC Mol Biol. 2009 Jul 23;10:72
references: 19624860
references: Brain Res Mol Brain Res. 2001 Nov 30;96(1-2):77-81
references: 11731011
references: PLoS One. 2007 May 09;2(5):e431
references: 17487276
references: Neuroscience. 2006;139(3):1017-29
references: 16500030
references: Biochemistry (Mosc). 2002 Apr;67(4):451-5
references: 11996659