Phencyclidine rapidly decreases neuronal mRNA of brain-derived neurotrophic factor

Yusuke Katanuma, Tadahiro Numakawa, Naoki Adachi, Noriko Yamamoto, Yoshiko Ooshima, Odaka Haruki, Inoue Takafumi, Hiroshi Kunugi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalSynapse
Volume68
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • BDNF
  • NMDA receptor
  • Phencyclidine
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Katanuma, Y., Numakawa, T., Adachi, N., Yamamoto, N., Ooshima, Y., Haruki, O., Takafumi, I., & Kunugi, H. (2014). Phencyclidine rapidly decreases neuronal mRNA of brain-derived neurotrophic factor. Synapse, 68(6), 257-265. https://doi.org/10.1002/syn.21735