PMID- 23912236 OWN - NLM STAT- MEDLINE DCOM- 20140407 LR - 20211021 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 14 IP - 8 DP - 2013 Jul 31 TI - Effect of delta-opioid receptor activation on BDNF-TrkB vs. TNF-alpha in the mouse cortex exposed to prolonged hypoxia. PG - 15959-76 LID - 10.3390/ijms140815959 [doi] AB - We investigated whether delta-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-alpha 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-alpha in the cortex, while DOR activation up-regulates BDNF-TrkB signaling thereby decreasing TNF-alpha levels in the hypoxic cortex. FAU - Tian, Xuesong AU - Tian X AD - The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA. xuesong.tian@uth.tmc.edu FAU - Hua, Fei AU - Hua F FAU - Sandhu, Harleen K AU - Sandhu HK FAU - Chao, Dongman AU - Chao D FAU - Balboni, Gianfranco AU - Balboni G FAU - Salvadori, Severo AU - Salvadori S FAU - He, Xiaozhou AU - He X FAU - Xia, Ying AU - Xia Y LA - eng GR - R01 AT004422/AT/NCCIH NIH HHS/United States GR - R01 HD034852/HD/NICHD NIH HHS/United States GR - AT-004422/AT/NCCIH NIH HHS/United States GR - HD-034852/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130731 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1H-benzimidazol-2-yl)(carboxymethyl)methylamide) RN - 0 (Activating Transcription Factor 1) RN - 0 (Atf1 protein, mouse) RN - 0 (Benzimidazoles) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CD11b Antigen) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Oligopeptides) RN - 0 (Receptors, Opioid, delta) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, mouse) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Activating Transcription Factor 1/metabolism MH - Animals MH - Benzimidazoles/pharmacology MH - Brain-Derived Neurotrophic Factor/biosynthesis/*metabolism MH - CD11b Antigen/metabolism MH - CREB-Binding Protein/metabolism MH - Cerebellar Cortex/metabolism MH - Cerebral Cortex/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Down-Regulation MH - Hypoxia/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/metabolism MH - Neurons/metabolism MH - Oligopeptides/pharmacology MH - Receptor, trkB/*metabolism MH - Receptors, Opioid, delta/agonists/*metabolism MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/*metabolism MH - Up-Regulation PMC - PMC3759895 EDAT- 2013/08/06 06:00 MHDA- 2014/04/08 06:00 PMCR- 2013/08/01 CRDT- 2013/08/06 06:00 PHST- 2013/06/19 00:00 [received] PHST- 2013/07/25 00:00 [revised] PHST- 2013/07/25 00:00 [accepted] PHST- 2013/08/06 06:00 [entrez] PHST- 2013/08/06 06:00 [pubmed] PHST- 2014/04/08 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - ijms140815959 [pii] AID - ijms-14-15959 [pii] AID - 10.3390/ijms140815959 [doi] PST - epublish SO - Int J Mol Sci. 2013 Jul 31;14(8):15959-76. doi: 10.3390/ijms140815959.