Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden

被引:14
作者
Giridharan, Vijayasree V. [1 ]
Catumbela, Celso S. G. [2 ]
Catalao, Carlos Henrique R. [1 ,3 ]
Lee, Juneyoung [2 ]
Ganesh, Bhanu P. [2 ]
Petronilho, Fabricia [4 ]
Dal-Pizzol, Felipe [4 ]
Morales, Rodrigo [2 ,5 ]
Barichello, Tatiana [1 ,4 ]
机构
[1] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Faillace Dept Psychiat & Behav Sci, Houston, TX 77030 USA
[2] Univ Texas Hlth Sci Ctr Houston UTHlth, McGovern Med Sch, Dept Neurol, Houston, TX USA
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Ribeirao Preto, SP, Brazil
[4] Univ Southern Santa Catarina UNESC, Grad Program Hlth Sci, Criciuma, SC, Brazil
[5] Univ Bernardo OHiggins, Ctr Integrat Biol & Quim Aplicada CIBQA, Santiago, Chile
基金
巴西圣保罗研究基金会;
关键词
CHAIN FATTY-ACIDS; MOUSE MODEL; COGNITIVE IMPAIRMENT; MOLECULAR-PSYCHIATRY; GLOBAL BURDEN; INFLAMMATION; BRAIN; LIPOPOLYSACCHARIDE; INFECTIONS; DYSBIOSIS;
D O I
10.1038/s41380-023-02172-2
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
While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble A & beta; increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of A & beta; dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 & mu;m near A & beta; deposits in the brain. In the gut, sepsis negatively modulated the & alpha;- and & beta;-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.
引用
收藏
页码:4463 / 4473
页数:11
相关论文
共 50 条
[41]   Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer's disease mice [J].
Zhang, Lingxiao ;
Hou, Shengjie ;
Movahedi, Fatemeh ;
Li, Zijin ;
Li, Li ;
Hu, Jing ;
Jia, Yingbo ;
Huang, Yaru ;
Zhu, Jie ;
Sun, Xiaoying ;
Zeng, Linghui ;
Liu, Ruitian ;
Xu, Zhi Ping .
NANO TODAY, 2023, 49
[42]   Inflammation, negative affect, and amyloid burden in Alzheimer's disease: Insights from the kynurenine pathway [J].
Willette, Auriel A. ;
Pappas, Colleen ;
Hoth, Nathan ;
Wang, Qian ;
Klinedinst, Brandon ;
Willette, Sara A. ;
Larsen, Brittany ;
Pollpeter, Amy ;
Li, Tianqi ;
Le, Scott ;
Collazo-Martinez, Ana D. ;
Mochel, Jonathan P. ;
Allenspach, Karin ;
Dantzer, Robert .
BRAIN BEHAVIOR AND IMMUNITY, 2021, 95 :216-225
[43]   Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer's disease mouse model [J].
Freitag, Kiara ;
Sterczyk, Nele ;
Wendlinger, Sarah ;
Obermayer, Benedikt ;
Schulz, Julia ;
Farztdinov, Vadim ;
Muelleder, Michael ;
Ralser, Markus ;
Houtman, Judith ;
Fleck, Lara ;
Braeuning, Caroline ;
Sansevrino, Roberto ;
Hoffmann, Christian ;
Milovanovic, Dragomir ;
Sigrist, Stephan J. ;
Conrad, Thomas ;
Beule, Dieter ;
Heppner, Frank L. ;
Jendrach, Marina .
JOURNAL OF NEUROINFLAMMATION, 2022, 19 (01)
[44]   Chronic Noise Exposure Acts Cumulatively to Exacerbate Alzheimer's Disease-Like Amyloid-β Pathology and Neuroinflammation in the Rat Hippocampus [J].
Cui, Bo ;
Li, Kang ;
Gai, Zhihui ;
She, Xiaojun ;
Zhang, Na ;
Xu, Chuanxiang ;
Chen, Xuewei ;
An, Gaihong ;
Ma, Qiang ;
Wang, Rui .
SCIENTIFIC REPORTS, 2015, 5
[45]   Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer's disease-like neuroinflammation triggered by periodontal disease [J].
Zhao, Chuanjiang ;
Kuraji, Ryutaro ;
Ye, Changchang ;
Gao, Li ;
Radaic, Allan ;
Kamarajan, Pachiyappan ;
Taketani, Yoshimasa ;
Kapila, Yvonne L. .
JOURNAL OF NEUROINFLAMMATION, 2023, 20 (01)
[46]   A Bibliometric Review on Gut Microbiome and Alzheimer's Disease Between 2012 and 2021 [J].
Trejo-Castro, Alejandro I. ;
Carrion-Alvarez, Diego ;
Martinez-Torteya, Antonio ;
Rangel-Escareno, Claudia .
FRONTIERS IN AGING NEUROSCIENCE, 2022, 14
[47]   The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease [J].
Askarova, Sholpan ;
Umbayev, Bauyrzhan ;
Masoud, Abdul-Razak ;
Kaiyrlykyzy, Aiym ;
Safarova, Yuliya ;
Tsoy, Andrey ;
Olzhayev, Farkhad ;
Kushugulova, Almagul .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2020, 10
[48]   Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer's disease [J].
Goyal, Divya ;
Ali, Syed Afroz ;
Singh, Rakesh Kumar .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2021, 106
[49]   Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation [J].
Raha, Animesh Alexander ;
Ghaffari, Seyedeh Deniz ;
Henderson, James ;
Chakraborty, Subhojit ;
Allinson, Kieren ;
Friedland, Robert P. ;
Holland, Anthony ;
Zaman, Shahid H. ;
Mukaetova-Ladinska, Elizabeta B. ;
Raha-Chowdhury, Ruma .
FRONTIERS IN AGING NEUROSCIENCE, 2021, 13
[50]   Choroid Plexus Volume, Amyloid Burden, and Cognition in the Alzheimer's Disease Continuum [J].
Jeong, Seong Ho ;
Park, Chae Jung ;
Cha, Jungho ;
Kim, Sang-Young ;
Lee, Seung-Koo ;
Kim, Yun Joong ;
Sohn, Young H. ;
Chung, Seok Jong ;
Lee, Phil Hyu .
AGING AND DISEASE, 2025, 16 (01) :552-564