机构：[1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea[2]Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea[3]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea[4]Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea[5]Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, South Korea[6]Department of Anesthesiology, The First People’s Hospital of Yunnan Province. The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China外科片麻醉手术科云南省第一人民医院[7]Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, South Korea[8]Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Sejong, South Korea[9]Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea[10]Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea
Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18 -20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 +/- 0.19, LPS = 2.57 +/- 0.08). However, gene expression of the pro-inflammatory cytokine IL-1 beta was increased (RT-PCR, control = 1.00 +/- 0.30; LPS = 2.01 +/- 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.
基金：
National Research Foundation of Korea [NRF-2018R1C1B6003139, NRF- 2019M3E5D1A02068575, NRF-2022R1A2C2006269, NRF-2022R1A2C2002756]; Korean ministry of health and welfare [HR22C1734]
第一作者机构：[1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea[2]Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea[3]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea
通讯作者：
通讯机构：[1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea[2]Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea[3]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea[4]Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea[5]Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, South Korea[7]Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, South Korea[10]Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea[*1]Department of Medical Science, Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, South Korea[*2]Department of Medical Science, Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea.
推荐引用方式(GB/T 7714)：
Lee Yulim,Ju Xianshu,Cui Jianchen,et al.Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice[J].HELIYON.2024,10(7):doi:10.1016/j.heliyon.2024.e28974.
APA：
Lee, Yulim,Ju, Xianshu,Cui, Jianchen,Zhang, Tao,Hong, Boohwi...&Chung, Woosuk.(2024).Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice.HELIYON,10,(7)
MLA：
Lee, Yulim,et al."Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice".HELIYON 10..7(2024)
