Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China.
Nat Commun. 2024 Nov 28;15(1):10361. doi: 10.1038/s41467-024-54827-5.
As the ability of liver regeneration is pivotal for liver disease patients, it will be of high significance and importance to identify the missing piece of the jigsaw influencing the liver regeneration. Here, we report that chronic stress impairs the liver regeneration capacity after partial hepatectomy with increased mortality in male mice. Anatomical tracing and functional mapping identified a neural circuit from noradrenergic neurons in the locus coeruleus (LC) to serotonergic neurons in the rostral medullary raphe region (rMR), which critically contributes to the inhibition of liver regeneration under chronic stress. In addition, hepatic sympathetic nerves were shown to be critical for the inhibitory effects on liver regeneration by releasing norepinephrine (NE), which acts on adrenergic receptor β2 (ADRB2) to block the proinflammatory macrophage activation. Collectively, we reveal a "brain-to-liver" neural connection that mediates chronic stress-evoked deficits in liver regeneration, thus shedding important insights into hepatic disease therapy.
由于肝脏再生能力对肝病患者至关重要，因此确定影响肝脏再生的关键拼图缺失部分将具有重要意义。在这里，我们报告慢性应激会损害雄性小鼠部分肝切除术后的肝脏再生能力，并增加其死亡率。解剖追踪和功能映射确定了一个从蓝斑核（LC）中的去甲肾上腺素能神经元到中脑嘴侧被盖区（rMR）中的 5-羟色胺能神经元的神经回路，该神经回路对慢性应激下的肝脏再生抑制起关键作用。此外，肝交感神经通过释放去甲肾上腺素（NE）对肝脏再生的抑制作用至关重要，去甲肾上腺素作用于肾上腺素能受体β2（ADRB2）以阻止促炎巨噬细胞的激活。总之，我们揭示了一种“脑-肝”神经连接，介导慢性应激引起的肝脏再生缺陷，从而为肝脏疾病治疗提供了重要的见解。
