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

Xuesong Tian¹  Fei Hua⁴  Harleen K Sandhu¹  Dongman Chao¹  Gianfranco Balboni²  Severo Salvadori³  Xiaozhou He⁴ 

[1] The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA; E-Mails:;Department of Life and Environment Sciences, University of Cagliari, Cagliari I-09124, Italy; E-Mail:;Department of Pharmaceutical Sciences, University of Ferrara, Ferrara I-44100, Italy; E-Mail:;Research Institute of Modern Medicine, The Third Medical College of Soochow University, Changzhou, Jiangsu 213002, China; E-Mail:

关键词: δ-opioid receptor;    brain-derived neurotrophic factor (BDNF);    TNF-α;    hypoxia;    neuroprotection;   

DOI  :  10.3390/ijms140815959

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland