Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice
Jiayi Zhao,Wei Bi,Shu Xiao,Xin Lan,Xiaofeng Cheng,Jiawei Zhang,Daxiang Lu,Wei Wei,Yanping Wang,Hongmei Li,Yong-Mei Fu,Lihong Zhu +11 more
TLDR
The data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections are compared.Abstract:
In this study, we investigated lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6J mice by using behavioral tests, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Western blot. We found that LPS treatment leads to sickness behavior and cognitive impairment in mice as shown in the Morris water maze and passive avoidance test, and these effects were accompanied by microglia activation (labeled by ionized calcium binding adaptor molecule-1, IBA-1) and neuronal cell loss (labeled by microtubule-associated protein 2, MAP-2) in the hippocampus. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the serum and brain homogenates were reduced by the LPS treatment, while the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE2) and nitric oxide (NO) were increased. In addition, LPS promoted the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the brain homogenates. The Western blot analysis showed that the nuclear factor kappa B (NF-κB) signaling pathway was activated in the LPS groups. Furthermore, VIPER, which is a TLR-4-specific inhibitory peptide, prevented the LPS-induced neuroinflammation and cognitive impairment. These data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, we compared the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections of LPS in LPS-induced neuroinflammation and cognitive impairment, and these data may provide additional insight for researchers performing neuroinflammation research.read more
Citations
More filters
Journal ArticleDOI
ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease.
TL;DR: It is suggested that future studies should focus on targeted manipulation of NOX in the microglia to understand the molecular mechanisms driving inflammatory-related NOX activation and recent evidence that therapeutic target identification should be unbiased and founded on relevant pathophysiological assays to facilitate the discovery of translatable antioxidant and anti-inflammatory therapeutics.
Journal ArticleDOI
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.
TL;DR: As aging together with poor diet and gut-derived inflammatory response due to dysbiosis contributes to the pathogenesis of AD, modification of gut microbial composition by uptake of probiotic-rich food can act as a preventive/therapeutic option for AD.
Journal ArticleDOI
Gut microbial molecules in behavioural and neurodegenerative conditions.
TL;DR: Bacterial metabolites with known or suspected neuromodulatory activity are described, mechanisms of signalling pathways from the gut microbiota to the brain are defined and direct effects that gut bacterial molecules are likely exerting on specific brain cells are discussed.
Journal ArticleDOI
Signaling inflammation across the gut-brain axis.
TL;DR: The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, and responding to signals derived from the internal and external environment as mentioned in this paper, and they are the sensory organs that detect, relay, integrate, and respond to signals from the external environment.
Journal ArticleDOI
Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.
Kanmani Suganya,Byung-Soo Koo +1 more
TL;DR: This review summarizes the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders and highlights the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the Gut–brain axis.
References
More filters
Journal ArticleDOI
Developments of a water-maze procedure for studying spatial learning in the rat
TL;DR: Developments of an open-field water-maze procedure in which rats learn to escape from opaque water onto a hidden platform are described, suggesting that they may lend themselves to a variety of behavioural investigations, including pharmacological work and studies of cerebral function.
Journal ArticleDOI
From inflammation to sickness and depression: when the immune system subjugates the brain
TL;DR: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour, which can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals.
Journal ArticleDOI
Inflammation and Alzheimer's disease.
Haruhiko Akiyama,Steven W. Barger,Scott R. Barnum,B Bradt,Jürgen Bauer,Greg M. Cole,Neil R. Cooper,Piet Eikelenboom,Mark R. Emmerling,Bernd L. Fiebich,Caleb E. Finch,Sally A. Frautschy,W. S. T. Griffin,Harald Hampel,Michael Hüll,Gary E. Landreth,Lih-Fen Lue,Robert E. Mrak,Ian R. A. Mackenzie,Patrick L. McGeer,M K O'Banion,Joel S. Pachter,Giulio Maria Pasinetti,C Plata-Salaman,Joseph G. Rogers,Russell E. Rydel,Yueyang Shen,Wolfgang J. Streit,Ronald Strohmeyer,I Tooyoma,F L van Muiswinkel,R. Veerhuis,David G. Walker,Scott D. Webster,Beatrice Hauss–Wegrzyniak,Gary L. Wenk,Tony Wyss-Coray +36 more
TL;DR: By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.
Journal ArticleDOI
Mechanisms underlying inflammation in neurodegeneration.
TL;DR: There is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators in neurodegenerative diseases.
Journal ArticleDOI
Reactive microglia are positive for HLA‐DR in the substantia nigra of Parkinson's and Alzheimer's disease brains
TL;DR: The detected large numbers of HLA-DR-positive reactive microglia (macrophages) in the substantia nigra of all cases studied with Parkinson's disease and parkinsonism and suggest a frequent coexistence of DAT- and Parkinson-type pathology in elderly patients.
Related Papers (5)
Neuroinflammation in Alzheimer's disease
Michael T. Heneka,Monica J. Carson,Joseph El Khoury,Gary E. Landreth,Frederic Brosseron,Douglas L. Feinstein,Andreas H. Jacobs,Tony Wyss-Coray,Tony Wyss-Coray,Javier Vitorica,Richard M. Ransohoff,Karl Herrup,Sally A. Frautschy,Bente Finsen,Guy C. Brown,Alexei Verkhratsky,Alexei Verkhratsky,Alexei Verkhratsky,Koji Yamanaka,Jari Koistinaho,Eicke Latz,Eicke Latz,Annett Halle,Gabor C. Petzold,Terrence Town,Dave Morgan,Mari L. Shinohara,V. Hugh Perry,Clive Holmes,Clive Holmes,Nicolas G. Bazan,David J. Brooks,Stéphane Hunot,Bertrand Joseph,Nikolaus Deigendesch,Olga Garaschuk,Erik Boddeke,Charles A. Dinarello,John C.S. Breitner,Greg M. Cole,Douglas T. Golenbock,Markus P. Kummer +41 more
Neurotoxic reactive astrocytes are induced by activated microglia
Shane A. Liddelow,Kevin A. Guttenplan,Laura E. Clarke,Frederick C. Bennett,Christopher J. Bohlen,Lucas Schirmer,Mariko L. Bennett,Alexandra E. Münch,Won-Suk Chung,Todd C. Peterson,Daniel K. Wilton,Arnaud Frouin,Brooke A. Napier,Nikhil Panicker,Manoj Kumar,Marion S. Buckwalter,David H. Rowitch,Valina L. Dawson,Ted M. Dawson,Beth Stevens,Ben A. Barres +20 more