論文 - 詳細
| RRC ID | 88273 |
|---|---|
| 著者 | Tran TV, Park SJ, Shin EJ, Tran HQ, Jeong JH, Jang CG, Lee YJ, Nah SY, Nabeshima T, Kim HC. |
| タイトル | Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB. |
| ジャーナル | Brain Res Bull |
| 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. |
| 巻・号 | 137 |
| ページ | 71-78 |
| 公開日 | 2018-3-1 |
| DOI | 10.1016/j.brainresbull.2017.11.004 |
| PII | S0361-9230(17)30552-X |
| PMID | 29122692 |
| MeSH | Animals Antipsychotic Agents / pharmacology* Disease Models, Animal Down-Regulation / drug effects Ginkgolides / pharmacology* Hippocampus / drug effects Hippocampus / metabolism Hippocampus / pathology Lactones / pharmacology* Mice, Inbred C57BL Mice, Knockout NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism* Phencyclidine / toxicity* Platelet Membrane Glycoproteins / antagonists & inhibitors* Platelet Membrane Glycoproteins / genetics Platelet Membrane Glycoproteins / metabolism Prefrontal Cortex / drug effects Prefrontal Cortex / metabolism Prefrontal Cortex / pathology Psychoses, Substance-Induced / drug therapy* Psychoses, Substance-Induced / metabolism Psychoses, Substance-Induced / pathology Psychoses, Substance-Induced / psychology Pyrrolidines / pharmacology RNA, Messenger / metabolism Receptors, G-Protein-Coupled / antagonists & inhibitors* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Thiocarbamates / pharmacology |
| IF | 3.37 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01733 |