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P2‐099: Lipidome of human microdissected senile plaques: Increased level of long‐chain saturated ceramides
Author(s) -
Panchal Maï,
Gaudin Mathieu,
Rivals Isabelle,
Lazar Adina,
Ayciriex Sophie,
Auzeil Nicolas,
Laprevote Olivier,
Duyckaerts Charles
Publication year - 2012
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.2012.05.2145
Subject(s) - lipidome , neuropil , senile plaques , chemistry , glycerophospholipids , phosphatidylethanolamine , biochemistry , pathology , biology , lipidomics , membrane , alzheimer's disease , endocrinology , phospholipid , phosphatidylcholine , medicine , disease , central nervous system
Background: Aß oligomers are suspected to have an exquisite toxicity and to play a key role in Alzheimer’s disease. However, up to now, the mechanisms by which they cause cognitive impairment remains widely unknown. Our study addresses the question of the functional and structural correlates of A ß oligomers toxicity. Methods: We used a well characterized type of synthetic Aß oligomers (termed as ADDLs for Aß derived diffusible ligands) which toxicity has already been established in vitro. We stereotactically injected these ADDLs tagged with fluor-hylite 555 (n 1⁄4 18 mice) or a vehicle solution (control group, n 1⁄4 17) in the right hippocampus of C57Bl6 mice. We analyzed 6 days after surgery the short-term spatial recognition memory of the injected mice (alternation paradigm in a Y-maze). Mice were sacrificed 24 hours later and their brain processed for immunohistochemistry. Synaptophysin and PSD95 labeling was analyzed to assess preand post-synaptic integrity. In a subset of 15 additionalmicewemapped brain fos expression to evaluate post-stimulation neuronal activity and its modulation by ADDLs.Results: Six days after an acute hippocampal injection the ADDLs elicited a specific abolition of short term spatial memory (comparison with performance of vehicle-injected mice, p < 0.01). Histologically, we observed a decrease in the relative optical density of the synaptophysin and PSD95 staining in ADDLs injected mice, not only at the site of injection but also at distance, for instance in the frontal lobes of the animals (comparison with vehicle-injected mice, p<0.05). In contrast, fos labeling was largely increased in ADDLs injected mice especially in the frontal lobe suggesting some compensatory mechanisms (comparison with vehicle-injected mice, p<0.001). Conclusions: Our study demonstrates for the first time the possible link between the behavioral deficits induced by Aß oligomers injections and underlying structural lesions. In particular we observed in Aß oligomers injected mice widespread synaptic anomalies which strikingly parallel memory impairments.