前頭前皮質のmiR-874-3pはIDO1抑制を介してLPS誘発性のうつ様行動を緩解する
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- 國澤 和生
- 藤田医科大・院保健・レギュラトリーサイエンス
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- Suento Willy Jaya
- 藤田医科大・院保健・病態制御解析学 Hasanuddin University・Faculty of Medicine・Department of Psychiatry
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- Wulaer Bolati
- 藤田医科大・院保健・病態制御解析学 藤田医科大・院保健・先進診断システム
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- 小菅 愛加
- 藤田医科大・院保健・レギュラトリーサイエンス
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- 飯田 翼
- 藤田医科大・院保健・レギュラトリーサイエンス
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- 藤垣 英嗣
- 藤田医科大・院保健・病態制御解析学
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- 山本 康子
- 藤田医科大・院保健・病態制御解析学
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- Tanra Andi Jayalangkara
- Hasanuddin University・Faculty of Medicine・Department of Psychiatry
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- 齋藤 邦明
- 藤田医科大・院保健・病態制御解析学 藤田医科大・院保健・先進診断システム 特定非営利活動法人 医薬品適正使用推進機構
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- 鍋島 俊隆
- 藤田医科大・院保健・先進診断システム 特定非営利活動法人 医薬品適正使用推進機構
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- 毛利 彰宏
- 藤田医科大・院保健・レギュラトリーサイエンス 特定非営利活動法人 医薬品適正使用推進機構
書誌事項
- タイトル別名
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- Prefrontal cortex miR-874-3p prevents lipopolysaccharide-induced depression-like behavior through inhibition of indoleamine 2,3-dioxygenase 1 expression in mice
- Prefrontal cortex miR‐874‐3p prevents lipopolysaccharide‐induced depression‐like behavior through inhibition of indoleamine 2,3‐dioxygenase 1 expression in mice
この論文をさがす
説明
<p>Indoleamine 2,3-dioxygenase 1 (IDO1) is the first rate-limiting enzyme that metabolizes tryptophan to the kynurenine pathway. Its activity is highly inducible by pro-inflammatory cytokines and correlates with the severity of major depressive disorder (MDD). MicroRNAs (miRNAs) are involved in gene regulation and the development of neuropsychiatric disorders including MDD. However, the role of miRNAs in targeting IDO1 in the pathophysiology of MDD is still unknown. In the present study, we investigated the role of novel miRNAs in the regulation of IDO1 activity and its effect on lipopolysaccharide (LPS)-induced depression-like behavior in mice. LPS upregulated miR-874-3p concomitantly with increase of IDO1 expression in the prefrontal cortex (PFC), increase of immobility in the forced swimming test as depression-like behavior and decrease of locomotor activity as sickness behavior without motor dysfunction. The miR-874-3p increased in both neuron and microglia after LPS. Its mimic significantly suppressed LPS-induced IDO1 expression in the PFC. Infusion of IDO1 inhibitor (1-methyl-l-tryptophan) and miR-874-3p into PFC prevented an increase of immobility in the forced swimming test, but did not decrease of locomotor activity induced by LPS. These results suggest that miR-874-3p may play an important role in preventing the LPS-induced depression-like behavior through inhibition of IDO1 expression. This may also serve as a novel potential target molecule for the treatment of MDD.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 94 (0), 3-O-E1-3-, 2021
公益社団法人 日本薬理学会