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O2‐14‐01: Beta‐amyloid oligomers acutely induce memory deficits in association to tlr4‐mediated neuroinflammation
Author(s) -
Balducci Claudia
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.208
Subject(s) - neuroinflammation , microglia , tlr4 , hmgb1 , amyloid beta , memory impairment , inflammation , neuroscience , chemistry , knockout mouse , microbiology and biotechnology , medicine , receptor , biology , immunology , biochemistry , disease , cognition
Background:Beta-amyloid oligomers (AbOs) are recognized as the main responsible species of synaptic dysfunction in Alzheimer’s disease. We recently demonstrated that AbOs can induce memory loss upon single intracerebroventricular (ICV) injection in C57 na€ıve mice. Because of the intimate association between synaptic plasticity, memory formation and microglia, our main objectives were: 1. investigate whether single AbO injection lead to an activation of glial cells and release of pro-inflammatory cytokines; 2. considering that microglia activation in Alzhiemr’s disease seems to involve the toll like receptor-4 (TLR4) pathway, we also investigated its implication in mediating the AbO detrimental action on both memory and neuroinflammation.Methods:To test the AbO effect on neuroinflammation, they were ICV injected in C57mice and through immunohistochemistry and biochemistry glial activation and corresponding release of cytokines investigated at 2, 4, 8 and 24 hrs post-injection. Translocation of the high-mobility group box protein 1 (HMGB1), involved in cytokine release through TLR4, was also analysed. TLR4 knockout mice (TLR4) were ICV injected with AbOs and tested for their memory, in the novel object recognition test, and for glial cell activation as well. Results: We found that single AbO injection leading to memory impairment is also associated to 1. activation of glial cells; 2. increase of IL1b release and 3. translocation of HMGB1 into the cytoplasm. Importantly, anti-inflammatories reverted these phenomena. In addition, when AbOs were injected in TLR4mice their memory was preserved and inflammation prevented. Conclusions:Our data suggest that the AbO-mediated memory impairment may be linked to an activation of glial cells involving a TLR4-dependent pathway.