| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-03-07 |
| タイトル |
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タイトル |
Chronic diazepam administration increases the expression of Lcn2 in the CNS |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Furukawa, Tomonori
Shimoyama, Shuji
Miki, Yasuo
Nikaido, Yoshikazu
Koga, Kohei
Nakamura, Kazuhiko
Wakabayashi, Koichi
Ueno, Shinya
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| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neurophysiol |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Res Ctr Child Mental Dev |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neuropathol |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neurophysiol |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neurophysiol |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neurophysiol |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Res Ctr Child Mental Dev |
| 著者所属 |
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Hirosaki Univ, Grad Sch Med, Dept Neurophysiol |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Benzodiazepines (BZDs), which bind with high affinity to gamma-aminobutyric acid type A receptors (GABA(A)-Rs) and potentiate the effects of GABA, are widely prescribed for anxiety, insomnia, epileptic discharge, and as anticonvulsants. The long-term use of BZDs is limited due to adverse effects such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning. Additionally, clinical reports have shown that chronic BZD treatment increases the risk of Alzheimer's disease. Unusual GABA(A)-R subunit expression and GABA(A)-R phosphorylation are induced by chronic BZD use. However, the gene expression and signaling pathways related to these effects are not completely understood. In this study, we performed a microarray analysis to investigate the mechanisms underlying the effect of chronic BZD administration on gene expression. Diazepam (DZP, a BZD) was chronically administered, and whole transcripts in the brain were analyzed. We found that the mRNA expression levels were significantly affected by chronic DZP administration and that lipocalin 2 (Lcn2) mRNA was the most upregulated gene in the cerebral cortex, hippocampus, and amygdala. Lcn2 is known as an iron homeostasis-associated protein. Immunostained signals of Lcn2 were detected in neuron, astrocyte, microglia, and Lcn2 protein expression levels were consistently upregulated. This upregulation was observed without proinflammatory genes upregulation, and was attenuated by chronic treatment of deferoxamine mesylate (DFO), iron chelator. Our results suggest that chronic DZP administration regulates transcription and upregulates Lcn2 expression levels without an inflammatory response in the mouse brain. Furthermore, the DZP-induced upregulation of Lcn2 expression was influenced by ambient iron. |
| 書誌情報 |
PHARMACOLOGY RESEARCH & PERSPECTIVES
巻 5,
p. UNSP 00283,
発行日 2017-02
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
2052-1707 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.1002/prp2.283 |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 資源タイプ |
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値 |
Article |
prp2.283 (4.2 MB)
