Cited by 177Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsAnesthesia and Neurotoxicity Research

Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse

Kahn, Marielle S., Kranjac, Dinko, Alonzo, Chris A., Haase, Jennifer H., Cedillos, Rudy O., McLinden, Kristina A., Boehm, Gary W., Chumley, Michael J.·2012·Behavioural Brain Research

Abstract

Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of Aβ1-42, a peptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased Aβ1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased Aβ1-42 in the hippoca…

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Crossref · 10.1016/j.bbr.2012.01.010

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  • Chronic neuroinflammation has been shown to increase α-synuclein deposition in various synucleinopathy animal models.

    “Not only has chronic neuroinflammation been shown to increase α-synuclein deposition in various synucleinopathy animal models (51–56), but when these animals were treated with drugs to reduce neuroinflammation, α-synuclein neuropathology also decreased (57, 58).”

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Authors
Kahn, M. S., Kranjac, D., Alonzo, C. A., Haase, J. H., Cedillos, R. O., McLinden, K. A., Boehm, G. W., & Chumley, M. J.
Affiliations
Texas Christian University (US)
Corresponding author
Chumley, Michael J.
Venue
Behavioural Brain Research
Publisher
Elsevier BV
Published
2012-04
Volume
229
Issue
1
Pages
176-184
ISSN
0166-4328 (ISSN-L)
OpenAlex
W1981801578
Cited by
177
References
52
Citations by year
2026: 4 · 2025: 13 · 2024: 17 · 2023: 6 · 2022: 23 · 2021: 19 · 2020: 17 · 2019: 19 · 2018: 14 · 2017: 6 · 2016: 14 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 4
FWCI
5.36
Type
journal article
Language
en
Open access
closed
Locations
  • Behavioural Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords
Alzheimer's disease, amyloid-beta 42, hippocampus, lipopolysaccharide, endotoxin, peripheral inflammation, cognitive impairment, inflammatory cytokines, sickness behavior, endotoxin tolerance, Morris water maze, contextual fear conditioning, learning and memory
MeSH terms
Analysis of Variance, Animals, Cognition Disorders, Conditioning, Psychological, Drug Administration Schedule, Endotoxins, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Fear, Hippocampus, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Peptide Fragments, Time Factors, Weight Loss, Amyloid beta-Peptides, Maze Learning, Mice, Interleukin-1beta

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