Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model

被引:12
作者
Ji, Ming [1 ]
Gong, Wenliang [1 ]
Wang, Siman [1 ]
Zhang, Dianjun [1 ]
Chen, Binjie [1 ]
Li, Xinyu [1 ]
Wu, Xiafang [1 ]
Cui, Lulu [1 ]
Feng, Yuliang [1 ]
Verkhratsky, Alexei [1 ,2 ,3 ,4 ]
Li, Baoman [1 ]
机构
[1] China Med Univ, Sch Forens Med, Dept Forens Analyt Toxicol, Shenyang, Peoples R China
[2] Univ Manchester, Fac Biol Med & Hlth, Manchester, Lancs, England
[3] Ikerbasque, Achucarro Ctr Neurosci, E-48011 Bilbao, Spain
[4] State Res Inst Ctr Innovat Med, Dept Stem Cell Biol, LT-01102 Vilnius, Lithuania
基金
中国国家自然科学基金;
关键词
Astrocytes; Post-traumatic stress disorder; Leptin; STAT3; NLRP3; inflammasome; NEUROINFLAMMATION; HIPPOCAMPUS; IMPAIRMENT; EFFICACY; BEHAVIOR; THERAPY; CELLS; PTSD;
D O I
10.1007/s11064-022-03655-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Accumulating evidence suggests that the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome contributes to the pathophysiology of post-traumatic stress disorder (PTSD). Astrocytes, the homeostatic cells of the central nervous system are intimately involved into pathophysiology of various mental disorders including PTSD. We demonstrated previously that leptin exerts neuroprotection and ameliorates chronic sleep deprivation-induced depressive-like behaviours. Here, we extended the study of therapeutic effects of leptin to PTSD model mice. We discovered that PTSD is associated with significant activation of NLRP3 inflammasome in astrocytes sorted from GFAP-GFP transgenic mice, while administration of leptin markedly suppressed the activation of astrocytic NLRP3 inflammasome. Leptin effectively improved PTSD-associated behavioural alterations including fear memory, cognitive impairments, and depressive-like behaviours. Therapeutic effects of leptin were mediated by the signal transducer and activator of transcription 3 (STAT3) in astrocytes. In addition, the PTSD-related activation of NLRP3 inflammasome impairs astrocytic mitochondria suppressing ATP synthesis and leading to an increased ROS production. Leptin reversed mitochondrial inhibition by stimulating STAT3 in astrocytes. We propose leptin as a novel candidate for the pharmacological treatment of PTSD.
引用
收藏
页码:1180 / 1190
页数:11
相关论文
共 50 条
  • [31] Tempol prevents post-traumatic stress disorder induced memory impairment
    Alzoubi, Karem H.
    Rababa'h, Abeer M.
    Al Yacoub, Omar N.
    PHYSIOLOGY & BEHAVIOR, 2018, 184 : 189 - 195
  • [32] Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain Injury in Rats
    Ma, Jie
    Xiao, Wenjing
    Wang, Junrui
    Wu, Juan
    Ren, Jiandong
    Hou, Jun
    Gu, Jianwen
    Fan, Kaihua
    Yu, Botao
    INFLAMMATION, 2016, 39 (06) : 2094 - 2103
  • [33] Brexpiprazole blocks post-traumatic stress disorder-like memory while promoting normal fear memory
    Ducourneau, Eva-Gunnel
    Guette, Christelle
    Perrot, Damien
    Mondesir, Miguel
    Mombereau, Cedric
    Arnt, Jorn
    Desmedt, Aline
    Piazza, Pier-Vincenzo
    MOLECULAR PSYCHIATRY, 2021, 26 (07) : 3018 - 3033
  • [34] Role of ventral tegmental area dopamine neurons in fear memory retention in post-traumatic stress disorder model rats
    Huang, Chunzheng
    Lan, Qinghui
    Yan, Hongwei
    Huang, Baoyi
    Li, Shuihong
    Zhang, Changzheng
    Zhou, Peiling
    JOURNAL OF PSYCHIATRIC RESEARCH, 2024, 178 : 59 - 65
  • [35] The role of β-arrestin-2 on Fear/anxious-related memory in a rat model of Post-traumatic stress disorder
    Ding, Jinlan
    Han, Fang
    Wen, Lili
    Xiao, Bing
    Shi, Yuxiu
    JOURNAL OF AFFECTIVE DISORDERS, 2017, 213 : 1 - 8
  • [36] Vitamin C attenuates memory loss induced by post-traumatic stress like behavior in a rat model
    Alzoubi, Karem H.
    Shatnawi, Alaa F.
    Al-Qudah, Mohammad A.
    Alfaqih, Mahmoud A.
    BEHAVIOURAL BRAIN RESEARCH, 2020, 379
  • [37] Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder
    Vanuk, John R.
    Pace-Schott, Edward F.
    Bullock, Ayla
    Esbit, Simon
    Dailey, Natalie S.
    Killgore, William D. S.
    FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 2022, 16
  • [38] Dimethyl fumarate attenuates MSU-induced gouty arthritis by inhibiting NLRP3 inflammasome activation and oxidative stress
    Cao, Y.
    Hu, Y.
    Jin, X. -f.
    Liu, Y.
    Zou, J. -m.
    EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2023, 27 (02) : 628 - 641
  • [39] NEK7 Regulates NLRP3 Inflammasome Activation and Neuroinflammation Post-traumatic Brain Injury (vol 12, 202, 2019)
    Chen, Yuhua
    Meng, Jiao
    Bi, Fangfang
    Li, Hua
    Chang, Cuicui
    Ji, Chen
    Liu, Wei
    FRONTIERS IN MOLECULAR NEUROSCIENCE, 2019, 12
  • [40] Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-B activation
    Li, Xiuzhen
    Wang, Mengjun
    Hong, Hong
    Luo, Congjuan
    Liu, Zewei
    Yang, Ruiheng
    IMMUNOLOGIC RESEARCH, 2018, 66 (04) : 521 - 527