Bmal1在脂聚糖诱导的抑郁症类行为及其相关的"炎症风暴"中的潜在作用
Dan-Dan Xu1,2,3, Zhi-Qi Hou1,2,3, Ya-Yun Xu1,2,4
1School of Pharmacy, Anhui Medical University, 81 Mei-Shan Road, Hefei, 230032, Anhui, People's Republic of China.
概括
炎症通过扰乱昼夜节律和改变大脑和肌肉ARNT-1 (Bmal1) 样表达而诱导类似抑郁的行为. 抑制Bmal1扭转了这些LPS诱导的病理变化,这表明Bmal1
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
背景情况:
- 炎症与抑郁症的发病有关,但将其与昼夜节律功能障碍联系在一起的机制尚不清楚.
- 时钟基因,包括大脑和肌肉ARNT-like 1 (Bmal1),被怀疑会影响炎症和抑郁症的进展.
研究的目的:
- 调查昼夜钟基因,特别是Bmal1,在炎症和抑郁症之间的联系中的作用.
- 探索脂聚糖 (LPS) 挑战如何影响老鼠和BV2细胞的抑郁症类行为,炎症标记物和时钟基因表达.
主要方法:
- 在老鼠和BV2细胞中,用脂多糖 (LPS) 挑战诱导炎症和类似抑郁症的症状.
- 在BV2细胞中使用小干扰RNA (siRNA) 抑制了Bmal1的表达.
- 评估了类似抑郁症的行为,下丘脑-垂体-上腺 (HPA) 轴活动,质细胞激活,炎症性细胞因子水平和时钟基因表达.
主要成果:
- 在老鼠中,LPS诱导了类似抑郁症的行为",炎症风暴",HPA轴过度活跃,质激活和改变的细胞因子水平.
- 在LPS挑战下降了有益蛋白质 (BDNF,TREM1,Copine6,Syt-1) 和增加了海马和下丘脑中的TREM2.
- LPS改变了时钟基因表达 (减少了CLOCK,CRY2,PER2;改变了Bmal1),这些变化通过在BV2细胞中抑制Bmal1而逆转.
结论:
- 低血压症会诱导类似抑郁症的病理变化,部分由不平衡的Bmal1表达和昼夜节律功能障碍介导.
- Bmal1在炎症和抑郁症之间的相互作用中起着至关重要的作用,提供了潜在的治疗点.
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