Phencyclidine rapidly decreases neuronal mRNA of brain‐derived neurotrophic factor

摘要: Downregulation of brain-derived neurotrophic factor (BDNF), a member neurotrophin family, has been implicated in psychiatric diseases including schizophrenia. However, detailed mechanisms its reduction patients with schizophrenia remain unclear. Here, using cultured cortical neurons, we monitored BDNF mRNA levels following acute application phencyclidine [PCP; an N-methyl-d-aspartate (NMDA) receptor blocker], which is known to produce schizophrenia-like symptoms. We found that PCP rapidly caused total amount transcripts without effect on cell viability, while nerve growth was intact. Actinomycin-D (ActD), RNA synthesis inhibitor, decreased similar PCP, and coapplication ActD did not show further compared solo each drug. Among exons I, IV, VI, the exon positively regulated by neuronal activity, highly sensitive PCP. Furthermore, inactivated cAMP response element-binding protein (CREB; regulator transcriptional activity IV). The inactivation CREB also achieved inhibitor for Ca2+/calmodulin kinase II (CaMKII), although induced no inhibition activity. It possible decreases transcription via blocking NMDA receptor/CaMKII/CREB signaling. Synapse 68:257–265, 2014. © 2014 Wiley Periodicals, Inc.