Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB

The Vinh Tran, Se Jin Park, Eun Joo Shin, Hai Quyen Tran, Ji Hoon Jeong, Choon Gon Jang, Yu Jeung Lee, Seung Yeol Nah, Toshitaka Nabeshima, Hyoung Chun Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalBrain Research Bulletin
Volume137
DOIs
Publication statusPublished - 01-03-2018

Fingerprint

Phencyclidine
Platelet Activating Factor
Down-Regulation
ginkgolide B
Knockout Mice
Prefrontal Cortex
Hippocampus
Schizophrenia
platelet activating factor receptor
Up-Regulation
vpr Genes
Animal Models

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Tran, The Vinh ; Park, Se Jin ; Shin, Eun Joo ; Tran, Hai Quyen ; Jeong, Ji Hoon ; Jang, Choon Gon ; Lee, Yu Jeung ; Nah, Seung Yeol ; Nabeshima, Toshitaka ; Kim, Hyoung Chun. / Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB. In: Brain Research Bulletin. 2018 ; Vol. 137. pp. 71-78.
@article{de5e478a67f442c88804105f873a25c4,
title = "Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB",
abstract = "Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models.",
author = "Tran, {The Vinh} and Park, {Se Jin} and Shin, {Eun Joo} and Tran, {Hai Quyen} and Jeong, {Ji Hoon} and Jang, {Choon Gon} and Lee, {Yu Jeung} and Nah, {Seung Yeol} and Toshitaka Nabeshima and Kim, {Hyoung Chun}",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.brainresbull.2017.11.004",
language = "English",
volume = "137",
pages = "71--78",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier Inc.",

}

Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB. / Tran, The Vinh; Park, Se Jin; Shin, Eun Joo; Tran, Hai Quyen; Jeong, Ji Hoon; Jang, Choon Gon; Lee, Yu Jeung; Nah, Seung Yeol; Nabeshima, Toshitaka; Kim, Hyoung Chun.

In: Brain Research Bulletin, Vol. 137, 01.03.2018, p. 71-78.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB

AU - Tran, The Vinh

AU - Park, Se Jin

AU - Shin, Eun Joo

AU - Tran, Hai Quyen

AU - Jeong, Ji Hoon

AU - Jang, Choon Gon

AU - Lee, Yu Jeung

AU - Nah, Seung Yeol

AU - Nabeshima, Toshitaka

AU - Kim, Hyoung Chun

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models.

AB - Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models.

UR - http://www.scopus.com/inward/record.url?scp=85034583247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034583247&partnerID=8YFLogxK

U2 - 10.1016/j.brainresbull.2017.11.004

DO - 10.1016/j.brainresbull.2017.11.004

M3 - Article

C2 - 29122692

AN - SCOPUS:85034583247

VL - 137

SP - 71

EP - 78

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

ER -