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Effect of δ-Opioid Receptor Activation on BDNF-TrkB vs. TNF-α in the Mouse Cortex Exposed to Prolonged Hypoxia
The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA
Research Institute of Modern Medicine, The Third Medical College of Soochow University, Changzhou, Jiangsu 213002, China
Department of Life and Environment Sciences, University of Cagliari, Cagliari I-09124, Italy
Department of Pharmaceutical Sciences, University of Ferrara, Ferrara I-44100, Italy
* Authors to whom correspondence should be addressed.
Received: 19 June 2013; in revised form: 25 July 2013 / Accepted: 25 July 2013 / Published: 31 July 2013
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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Tian, X.; Hua, F.; Sandhu, H.K.; Chao, D.; Balboni, G.; Salvadori, S.; He, X.; Xia, Y. Effect of δ-Opioid Receptor Activation on BDNF-TrkB vs. TNF-α in the Mouse Cortex Exposed to Prolonged Hypoxia. Int. J. Mol. Sci. 2013, 14, 15959-15976.
Tian X, Hua F, Sandhu HK, Chao D, Balboni G, Salvadori S, He X, Xia Y. Effect of δ-Opioid Receptor Activation on BDNF-TrkB vs. TNF-α in the Mouse Cortex Exposed to Prolonged Hypoxia. International Journal of Molecular Sciences. 2013; 14(8):15959-15976.
Tian, Xuesong; Hua, Fei; Sandhu, Harleen K.; Chao, Dongman; Balboni, Gianfranco; Salvadori, Severo; He, Xiaozhou; Xia, Ying. 2013. "Effect of δ-Opioid Receptor Activation on BDNF-TrkB vs. TNF-α in the Mouse Cortex Exposed to Prolonged Hypoxia." Int. J. Mol. Sci. 14, no. 8: 15959-15976.