Chronic morphine intoxication reduces binding of HuD to BDNF long 3'-UTR, while morphine withdrawal stimulates BDNF expression in the frontal cortex of male Wistar rats.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) mediates opiate dependence phenomenon. In the brain of morphine dependent animals BDNF level is controlled transcriptionally, however, post-transcriptional mechanisms of BDNF regulation in this context remain unknown. Regulation of mRNA by binding of specific proteins to the 3'-untranslated region (3'-UTR) is one of such mechanisms. Among RNA-binding proteins neuronal Hu antigen D (HuD) is the best characterized positive regulator of BDNF, however its involvement in opiate dependence remains obscure. We suggested that HuD binding to the BDNF 3'-UTR may be linked to changes in BDNF expression induced by morphine. The aim of this study was to investigate potential association of HuD with BDNF 3'-UTR in relation to BDNF expression (Exon- and 3'-UTR-specific mRNA variants and protein level) in the frontal cortex and midbrain of male Wistar rats after chronic morphine intoxication and spontaneous withdrawal in dependent animals.

RESULTS: After chronic morphine intoxication but not during morphine withdrawal HuD binding to the long BDNF 3'-UTR in the frontal cortex decreased as compared with the corresponding control group, however after intoxication BDNF expression did not change. The level of BDNF Exon I as well as mature BDNF polypeptide increased in the frontal cortex upon morphine withdrawal, while no changes in HuD binding could be detected.

CONCLUSION: Thus, contrary to the assumption, HuD-BDNF 3'-UTR interaction and BDNF expression in the frontal cortex differentially change in a manner dependent on the context of morphine action.