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: Xuesong Tian, Fei Hua, Harleen K Sandhu, Dongman Chao, Gianfranco Balboni, Severo Salvadori, Xiaozhou He, Ying Xia
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 8 Pg. 15959-76 (Jul 31 2013) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 23912236 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1H-benzimidazol-2-yl)(carboxymethyl)methylamide
• Activating Transcription Factor 1
• Atf1 protein, mouse
• Benzimidazoles
• Brain-Derived Neurotrophic Factor
• CD11b Antigen
• Creb1 protein, mouse
• Cyclic AMP Response Element-Binding Protein
• Oligopeptides
• Receptors, Opioid, delta
• Tumor Necrosis Factor-alpha
• CREB-Binding Protein
• Crebbp protein, mouse
• Receptor, trkB

Topics

• Activating Transcription Factor 1 (metabolism)
• Animals
• Benzimidazoles (pharmacology)
• Brain-Derived Neurotrophic Factor (biosynthesis, metabolism)
• CD11b Antigen (metabolism)
• CREB-Binding Protein (metabolism)
• Cerebellar Cortex (metabolism)
• Cerebral Cortex (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Down-Regulation
• Hypoxia (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Microglia (metabolism)
• Neurons (metabolism)
• Oligopeptides (pharmacology)
• Receptor, trkB (metabolism)
• Receptors, Opioid, delta (agonists, metabolism)
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation