Activation of tyrosine hydroxylase (TH) gene transcription induced by brain-derived neurotrophic factor (BDNF) and its selective inhibition through Ca2 signals evoked via the N-methyl-D-aspartate (NMDA) receptor

作者：Fukuchi Mamoru; Fujii Hiroaki; Takachi Haruna; Ichinose Hiroshi; Kuwana Yuki; Tabuchi Akiko; Tsuda Masaaki^*

来源：Brain Research, 2010, 1366: 18-26.

DOI：10.1016/j.brainres.2010.10.034

• Tyrosine hydroxylase
• Promoter assay
• BDNF
• NMDA receptor
• Calcium

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of catecholamine but its transcriptional regulation is not fully understood. Using a reporter assay with cultured rat cortical neurons, we demonstrated that the TH gene promoter was activated by brain-derived neurotrophic factor (BDNF), through its specific receptor TrkB and the ERK/MAP kinase pathway. Using a series of mutant TH gene promoters, we found that the cAMP-response element (CRE) plays a crucial role in the TH promoter activity and the Egr-1-responsive element (ERE), at least in part, is responsible for the BDNF-induced activation. Notably, the influx of Ca2 evoked via the N-methyl-D-aspartate receptor (NMDA-R) but not via the L-type voltage-dependent Ca2 channel (L-VDCC) selectively antagonized the activation of the gene promoter, suggesting a new link between the catecholaminergic and glutamatergic systems. The Ca2 signals evoked via NMDA-R did not affect the phosphorylation of ERK1/2 induced by BDNF. These results suggest that the TH gene's transcription is positively regulated by BDNF, through the CRE and ERE of the promoter, but selectively antagonized by the Ca2 signals evoked via NMDA-R without disturbing the ERK/MAP kinase pathway, the regulation by which may underlie the development of the catecholaminergic system in the brain.

• 出版日期2010-12-17