Neuronal MD2 induces long-term mental impairments in septic mice by facilitating necroptosis and apoptosis.
Neuronal MD2 induces long-term mental impairments in septic mice by facilitating necroptosis and apoptosis.
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神经元 MD2 通过促进坏死性凋亡和细胞凋亡诱导脓毒症小鼠长期精神损害
DOI：
10.3389/fphar.2022.884821
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhang, Xijing
中科院分区：
文献类型：
--
作者：
Fan, Zhongmin;Ma, Hongwei;Li, Yi;Wu, You;Wang, Jiajia;Xiong, Lize;Fang, Zongping;Zhang, Xijing
关键词：
脓毒症相关脑病（SAE）是脓毒症的并发症，发病率很高。SAE患者的长期心理健康问题导致生活质量大幅下降。然而，其潜在的机制尚不清楚，也没有有效的治疗方法。在本研究中，我们探讨细胞凋亡和坏死性凋亡在脓毒症中的作用。在盲肠结扎穿孔法（CLP）建立的脓毒症小鼠模型中，于第14天通过旷场、高架十字迷宫和强迫游泳实验检测到行为学改变。此外，凋亡和坏死相关蛋白和形态学变化进行了检查，在败血症小鼠海马。在CLP小鼠中检测到持久的抑郁样行为，以及神经元凋亡和坏死性凋亡的显著增加。重要的是，我们发现，细胞凋亡和坏死性凋亡是相关的，根据拉姆齐规则在脓毒症小鼠的大脑。抑制髓样分化因子2（MD2），细胞凋亡和坏死性凋亡的串扰介质，在神经元有效地减少神经元的损失，减轻败血症小鼠的抑郁样行为。这些结果表明，海马中的神经元死亡有助于SAE中的精神障碍，并且抑制神经元MD2是通过抑制坏死性凋亡和细胞凋亡来治疗脓毒症中的精神健康问题的新策略。
Sepsis-associated encephalopathy (SAE) is a complication of sepsis with high morbidity rates. Long-lasting mental health issues in patients with SAE result in a substantial decrease in quality of life. However, its underlying mechanism is unclear, and effective treatments are not available. In the current study, we explored the role of apoptosis and necroptosis related to mental dysfunction in sepsis. In a mouse model of sepsis constructed by cecal ligation and puncture (CLP), altered behavior was detected by the open field, elevated-plus maze and forced swimming tests on the fourteenth day. Moreover, apoptosis- and necroptosis-associated proteins and morphological changes were examined in the hippocampus of septic mice. Long-lasting depression-like behaviors were detected in the CLP mice, as well as significant increases in neuronal apoptosis and necroptosis. Importantly, we found that apoptosis and necroptosis were related according to Ramsay’s rule in the brains of the septic mice. Inhibiting myeloid differentiation factor 2 (MD2), the crosstalk mediator of apoptosis and necroptosis, in neurons effectively reduced neuronal loss and alleviated depression-like behaviors in the septic mice. These results suggest that neuronal death in the hippocampus contributes to the mental impairments in SAE and that inhibiting neuronal MD2 is a new strategy for treating mental health issues in sepsis by inhibiting necroptosis and apoptosis.
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影响因子：
9.3
作者：
Cao L;Mu W
通讯作者：
Mu W
影响因子：
3.8
作者：
Bolognese, Alexandra C.;Yang, Weng-Lang;Wang, Ping
通讯作者：
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影响因子：
2
作者：
Napolitano, Lena M.
通讯作者：
Napolitano, Lena M.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.3
作者：
Brites D;Fernandes A
通讯作者：
Fernandes A