title: Effect of δ-opioid receptor activation on BDNF-TrkB vs. TNF-α in the mouse cortex exposed to prolonged hypoxia.
abstract: We investigated whether δ-opioid receptor (DOR)-induced neuroprotection involves the brain-derived neurotrophic factor (BDNF) pathway. We studied the effect of DOR activation on the expression of BDNF and other proteins in the cortex of C57BL/6 mice exposed to hypoxia (10% of oxygen) for 1-10 days. The results showed that: (1) 1-day hypoxia had no appreciable effect on BDNF expression, while 3- and 10-day hypoxia progressively decreased BDNF expression, resulting in 37.3% reduction (p < 0.05) after 10-day exposure; (2) DOR activation with UFP-512 (1 mg/kg, i.p., daily) partially reversed the hypoxia-induced reduction of BDNF expression in the 3- or 10-day exposed cortex; (3) DOR activation partially reversed the hypoxia-induced reduction in functional TrkB (140-kDa) and attenuated hypoxia-induced increase in truncated TrkB (90-kDa) in the 3- or 10-day hypoxic cortex; and (4) prolonged hypoxia (10 days) significantly increased TNF-α level and decreased CD11b expression in the cortex, which was completely reversed following DOR activation; and (5) there was no significant change in pCREB and pATF-1 levels in the hypoxic cortex. We conclude that prolonged hypoxia down-regulates BDNF-TrkB signaling leading to an increase in TNF-α in the cortex, while DOR activation up-regulates BDNF-TrkB signaling thereby decreasing TNF-α levels in the hypoxic cortex.
authors.affiliation: The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA. xuesong.tian@uth.tmc.edu
authors.forename: Xuesong
authors.initials: X
authors.lastname: Tian
authors.forename: Fei
authors.initials: F
authors.lastname: Hua
authors.forename: Harleen K
authors.initials: HK
authors.lastname: Sandhu
authors.forename: Dongman
authors.initials: D
authors.lastname: Chao
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D020813:Receptor, trkB / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C526539:2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1H-benzimidazol-2-yl)(carboxymethyl)methylamide; D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D001562:Benzimidazoles; D019208:Brain-Derived Neurotrophic Factor; D039481:CD11b Antigen; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D014409:Tumor Necrosis Factor-alpha; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D020813:Receptor, trkB
references.citation: Nat Rev Drug Discov. 2011 Mar;10(3):209-19
references.pmid: 21358740
references.citation: Exp Neurol. 2005 Apr;192(2):265-73
references.pmid: 15755544
references.citation: Psychopharmacology (Berl). 2005 Nov;183(1):31-40
references.pmid: 16220339
references.citation: FEBS Lett. 2000 Dec 8;486(2):89-92
references.pmid: 11113444
references.citation: Neuroscience. 2012 Jan 27;202:352-62
references.pmid: 22200548
references.citation: PLoS One. 2010 Jul 23;5(7):e11746
references.pmid: 20668522
references.citation: Schizophr Bull. 2013 Jan;39(1):130-40
references.pmid: 21795612
references.citation: Brain Res. 2000 Dec 8;885(2):143-53
references.pmid: 11102568
references.citation: Peptides. 2008 Jan;29(1):93-103
references.pmid: 18069089
references.citation: Nature. 1997 Oct 23;389(6653):856-60
references.pmid: 9349818
references.citation: Eur J Neurosci. 2006 Feb;23(4):984-94
references.pmid: 16519663
references.citation: Annu Rev Neurosci. 2001;24:677-736
references.pmid: 11520916
references.citation: Acta Neuropathol. 2009 Jan;117(1):75-84
references.pmid: 18830614
references.citation: Prog Neurobiol. 2007 Apr;81(5-6):294-330
references.pmid: 17379385
references.citation: Neuropsychopharmacology. 2004 Apr;29(4):649-59
references.pmid: 14647482
references.citation: J Neuroinflammation. 2008 Oct 17;5:45
references.pmid: 18925972
references.citation: Neuroscience. 2010 May 5;167(2):256-60
references.pmid: 20156527
references.citation: Brain Res. 1998 Jun 29;797(2):278-86
references.pmid: 9666147
references.citation: Exp Neurol. 2003 Oct;183(2):469-81
references.pmid: 14552887
references.citation: Sheng Li Xue Bao. 2008 Aug 25;60(4):475-84
references.pmid: 18690389
references.citation: Int J Dev Neurosci. 2008 May-Jun;26(3-4):363-70
references.pmid: 18243629
references.citation: J Neuroimmune Pharmacol. 2013 Mar;8(1):66-78
references.pmid: 22367679
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4971-5
references.pmid: 8389459
references.citation: Exp Neurobiol. 2011 Jun;20(2):92-9
references.pmid: 22110366
references.citation: PLoS One. 2012;7(12):e51524
references.pmid: 23272113
references.citation: Front Biosci. 2004 Sep 01;9:3392-8
references.pmid: 15353366
references.citation: J Neuroimmunol. 2009 May 29;210(1-2):40-51
references.pmid: 19361871
references.citation: Ann Neurol. 2013 Jun;73(6):686-7
references.pmid: 23595639
references.citation: Int J Neurosci. 2013 Mar;123(3):191-5
references.pmid: 23110519
references.citation: PLoS One. 2013 Apr 15;8(4):e61080
references.pmid: 23596515
references.citation: Nat Med. 2002 Dec;8(12):1363-8
references.pmid: 12457181
references.citation: J Neuropathol Exp Neurol. 2006 Oct;65(10):945-52
references.pmid: 17021399
references.citation: J Med Chem. 2002 Dec 5;45(25):5556-63
references.pmid: 12459023
references.citation: Prog Neurobiol. 2010 Apr;90(4):439-70
references.pmid: 20036308
references.citation: Neuroscience. 2011 Jan 13;172:398-405
references.pmid: 21034794
references.citation: Science. 1993 Apr 9;260(5105):238-41
references.pmid: 8097062
references.citation: Br J Pharmacol. 2007 Dec;152(8):1312-24
references.pmid: 17982482
references.citation: BMC Biol. 2009 Jun 17;7:31
references.pmid: 19534760
references.citation: Eur J Neurosci. 2006 Jul;24(2):341-50
references.pmid: 16836639
references.citation: Science. 1999 Nov 12;286(5443):1358-62
references.pmid: 10558990
references.citation: Eur J Pharmacol. 2000 Feb 25;390(1-2):1-6
references.pmid: 10708700
references.citation: Neuroscience. 2012 May 17;210:363-74
references.pmid: 22426239
references.citation: Neuron. 2003 Aug 28;39(5):735-8
references.pmid: 12948441
references.citation: Neuroscience. 1997 May;78(2):431-48
references.pmid: 9145800
references.citation: Cell Mol Life Sci. 2013 Jul;70(13):2291-303
references.pmid: 23014992
references.citation: Brain Res. 2006 Jan 19;1069(1):172-81
references.pmid: 16364263
references.citation: Neuron. 1997 Nov;19(5):1031-47
references.pmid: 9390517