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P2‐320: Aβ oligomers and fibrils instigate the release of excitatory amino acids from hippocampal neurons
Author(s) -
Moreira Jordano Brito,
Paula Lima Andrea Cristina,
Bomfim Theresa R.,
Oliveira Fábio Figueiredo,
Sepúlveda Fernando J.,
Mello Fernando G.,
Aguayo Luis G.,
Panizzutti Rogério,
Ferreira Sérgio Teixeira
Publication year - 2010
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.2010.05.1371
Subject(s) - glutamate receptor , extracellular , excitatory postsynaptic potential , chemistry , nmda receptor , hippocampal formation , neurotoxicity , inhibitory postsynaptic potential , synaptic cleft , synaptic vesicle , biophysics , glutamatergic , biochemistry , microbiology and biotechnology , neuroscience , receptor , biology , vesicle , toxicity , organic chemistry , membrane
levels of CaN and pCREB in their hippocampus. Results: We found that CaN was increased and pCREB was significantly reduced in the hippocampus and cortex of AD patients and, to a lesser extent in MCI subjects as compared to non-demented individuals. Indeed there was a significant inverse correlation between pCREB levels and MMSE scores among AD patients, MCI subjects and normal individuals. Furthermore, icv injection of Ab oligomers that results in memory dysfunction in mice increased CaN and decreased pCREB, establishing a causal link between Ab-driven cognitive deficits and CaN hyper-activation. Conclusions: Collectively these results reveal that increased CaN activity may be central to Ab oligomer-induced memory deficits in AD and suggest it as a potential pharmacological target.