Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice

Journal of Neuroinflammation

Weixing Zhao¹  Yue Long¹  Xuan Zhang¹  Yitian Yang¹  Jiangbei Cao¹  Yishuang Wu¹  Zhipeng Xu¹  Weidong Mi¹  Xiaoying Zhang¹  Qiang Fu¹  Yunfeng Li² 

[1] Anesthesia and Operation Center, the First Medical Center, Chinese PLA General Hospital;State Key Laboratory of Toxicology Medical Countermeasures, Beijing Key Laboratories of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Academy of Military Sciences;

关键词: Elamipretide;    SS-31;    Antioxidant;    Mitochondrial dysfunction;    Oxidative stress;    Neuroinflammation;   

DOI  :  10.1186/s12974-019-1627-9

来源: DOAJ

【 摘 要 】

Abstract Background It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. Methods We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. Results Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. Conclusion These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.

【 授权许可】

Unknown