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Effect of δ-Opioid Receptor Activation on BDNF-TrkB vs. TNF-α in the Mouse Cortex Exposed to Prolonged Hypoxia
Authors:Xuesong Tian  Fei Hua  Harleen K Sandhu  Dongman Chao  Gianfranco Balboni  Severo Salvadori  Xiaozhou He  Ying Xia
Affiliation:1.The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA; E-Mails: (X.T.); (H.K.S.); (D.C.);2.Research Institute of Modern Medicine, The Third Medical College of Soochow University, Changzhou, Jiangsu 213002, China; E-Mail: ;3.Department of Life and Environment Sciences, University of Cagliari, Cagliari I-09124, Italy; E-Mail: ;4.Department of Pharmaceutical Sciences, University of Ferrara, Ferrara I-44100, Italy; E-Mail:
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.
Keywords:δ  -opioid receptor  brain-derived neurotrophic factor (BDNF)  TNF-α    hypoxia  neuroprotection
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