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Phencyclidine rapidly decreases neuronal mRNA of brain‐derived neurotrophic factor
Author(s) -
Katanuma Yusuke,
Numakawa Tadahiro,
Adachi Naoki,
Yamamoto Noriko,
Ooshima Yoshiko,
Odaka Haruki,
Inoue Takafumi,
Kunugi Hiroshi
Publication year - 2014
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21735
Subject(s) - creb , brain derived neurotrophic factor , neurotrophic factors , nmda receptor , phencyclidine , chemistry , neurotrophin , synapse , endocrinology , medicine , pharmacology , transcription factor , biology , receptor , microbiology and biotechnology , neuroscience , biochemistry , gene
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 Ca 2+ /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. Synapse 68:257–265, 2014 . © 2014 Wiley Periodicals, Inc.