Effect of δ-opioid receptor activation on BDNF-TrkB vs. TNF-α in the mouse cortex exposed to prolonged hypoxia.

We investigated whether δ -opioid receptor (DOR)-induced neuroprotection involves the brain-derived neur otrophic 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 eff ect on BDNF expression, wh ile 3- and 10-day hypoxia progressively decreased BDNF expression, resulting in 37.3% reduction ( p < 0.05) after 10-day exposure; (2) DOR activa tion with UFP-512 (1 mg/kg, i .p., daily) partially reversed the hypoxia-induced reductio n 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-indu ced increase in truncated Tr kB (90-kDa) in the 3- or 10-day hypoxic cortex; and (4) prolonged hypoxi a (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 concl ude 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