論文 - 詳細
| RRC ID | 47959 |
|---|---|
| 著者 | Chen H, He D, Lasek AW. |
| タイトル | Midkine in the mouse ventral tegmental area limits ethanol intake and Ccl2 gene expression. |
| ジャーナル | Genes Brain Behav |
| Abstract |
Midkine (MDK) is a cytokine and neurotrophic factor that is more highly expressed in the brains of alcoholics and in mice predisposed to drink large amounts of ethanol, suggesting that MDK may regulate ethanol consumption. Here we measured ethanol consumption in male and female Mdk knockout (-/-) mice using the two-bottle choice and the drinking in the dark (DID) tests. We found that Mdk -/- mice consumed significantly more ethanol than wild-type controls in both tests. To determine if MDK acts in the ventral tegmental area (VTA) to regulate ethanol consumption, we delivered lentivirus expressing a Mdk shRNA into the VTA of male C57BL/6J mice to locally knockdown Mdk and performed the DID test. Mice expressing a Mdk shRNA in the VTA consumed more ethanol than mice expressing a control non-targeting shRNA, demonstrating that the VTA is one site in the brain through which MDK acts to regulate ethanol consumption. Since MDK also controls the expression of inflammatory cytokines in other organs, we examined gene expression of interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfα) and the chemokine (C-C motif) ligand 2 (Ccl2) in the VTA of Mdk -/- mice and in mice expressing Mdk shRNA in the VTA. Expression of Ccl2 was elevated in the VTA of Mdk -/- mice and in mice expressing Mdk shRNA in the VTA. These results demonstrate that MDK functions in the VTA to limit ethanol consumption and levels of CCL2, a chemokine known to increase ethanol consumption. |
| 巻・号 | 16(7) |
| ページ | 699-708 |
| 公開日 | 2017-9-1 |
| DOI | 10.1111/gbb.12384 |
| PMID | 28398003 |
| PMC | PMC5595638 |
| MeSH | Alcohol Drinking / genetics* Alcohol Drinking / metabolism Animals Chemokine CCL2 / genetics Chemokine CCL2 / metabolism* Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Interleukin-1beta / genetics Interleukin-1beta / metabolism Male Mice Mice, Inbred C57BL Midkine Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Ventral Tegmental Area / metabolism* Ventral Tegmental Area / physiology |
| IF | 3.397 |
| 引用数 | 7 |
| 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 | RBRC02422 |