SIRT3 mitigates neuroinflammation and mitochondrial damage post-hypoxic-ischemic brain injury

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular immunology Pub Date : 2025-02-05 DOI:10.1016/j.molimm.2025.01.002

Ke Yan , Jiarong Bian , Liang He , Bingwei Song , Linhai Shen , Yong Zhen

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引用次数: 0

Abstract

Objective

We aimed to explore the role of SIRT3 in ameliorating neuroinflammation caused by hypoxia-ischemia (HI).

Methods

A rat model of HI was established, and 48 hours prior to constructing the HI model, the rats received an intracerebroventricular injection of a recombinant adeno-associated virus type 9 vector. TTC and Nissl staining assessed the effects of SIRT3 on cerebral infarction and brain atrophy in HI rats. Neuroinflammation was evaluated by investigating IL-1β and MPO positive cells, and ELISA for determining inflammatory cytokines. IBA-1, CD68, and iNOS positive microglia and NLRP3 activation-related protein expression were also detected. SIRT3 was overexpressed in oxygen glucose deprivation (OGD)-induced microglia model, where cell morphology and expressions of pro-inflammatory cytokines and NLRP3 inflammasome activation-related proteins were examined. Additionally, neurons co-cultured with SIRT3-overexpressing microglia were analyzed for mitochondrial damage and apoptosis.

Results

SIRT3 alleviated cerebral infarction and atrophy in HI rats. It also inhibited neuroinflammation, reducing IL-1β and MPO positive cells, and lowered the levels of pro-inflammatory cytokines. In both HI rat model and OGD cell model, SIRT3 inhibited excessive activation of microglia and NLRP3 inflammasome. Furthermore, co-culturing neurons with SIRT3-overexpressing microglia resulted in reduced neuronal apoptosis and improved mitochondrial function, evidenced by lower ROS levels, alleviated mitochondrial depolarization and increased ATP production.

Conclusion

SIRT3 restrains pro-inflammatory microglia and NLRP3 inflammasome and alleviates neuroinflammation following HI brain injury.

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.