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Chronic systemic inflammatory challenge induced by LPS promotes cognitive impairment
Author(s) -
Schirmbeck Gabriel Henrique,
Da Ré Carollina Fraga,
Seady Marina,
Fróes Fernanda,
Silva Sthefani Gomes,
Taday Jéssica Hauschild,
Gonçalves Carlos Alberto Saraiva,
Leite Marina Concli
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.557.3
Subject(s) - neuroinflammation , hippocampal formation , microglia , inflammation , dementia , systemic inflammation , memory impairment , open field , hippocampus , cognitive decline , glutamate receptor , medicine , neuroscience , endocrinology , psychology , disease , cognition , receptor
Neuroinflammation is a major component in the progression of neurodegenerative diseases such as dementia, although is not its main initiator. Its been demonstrated that inflammatory activation of microglia and astrocytes promotes protein aggregation of amyloid plaques and tau tangles, leading to neuronal death through other mechanisms, such as excitotoxicity. Although many studies investigated the effect of systemic inflammation on the progression of dementia and amyloid plaques in genetic mouse models of Alzheimer's disease, is not clear if systemic inflammation can induce dementia per se . Methods 90‐day Wistar rats were exposed to chronic inflammatory challenges with intraperitoneal injections of LPS in two doses (500 μg/kg and 250 μg/kg) or saline once a week, for a 16‐week period. Rats were euthanasied 24 h after last LPS injection. Behavioral evaluation was conducted through Open Field (OF) and Object Location Memory‐Test (OLM) for spatial memory assessment. Hippocampal S100B content was measured by ELISA, nuclear Nf‐κB was measured by western blot, and L‐[ 3 H] glutamate uptake was analyzed. Results Both groups receiving LPS presented impaired spatial memory in the 24 h OLM, which is characteristic of hippocampal degeneration in animal models of dementia, while OF shown no locomotor impairment. S100B protein remained unchanged between groups, and glutamate uptake was reduced only in LPS 500 μ/kg group. Nuclear fraction of Nf‐κB was increased in both LPS groups. Discussion Here, we demonstrate that chronic peripheral inflammatory stimuli promote cognitive impairment in the absence of other underlying neurodegenerative causes, such as genetic background. Increased Nf‐κB in nucleus indicates hippocampal neuroinflammation, despite LPS challenge being peripheral. Besides, glutamate uptake was reduced in the higher dose of LPS, indicating a possible excitotoxic damage. Conversely, S100B content, which is an important biomolecule in inflammatory signaling, was not affected by LPS. Support or Funding Information This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Apoio a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .