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P3–428: Stability of nicotinic acetylcholine receptor binding in the frontal and temporal cortex of subjects with mild cognitive impairment
Author(s) -
Trent DeKosky Steven,
Wecker Lynn,
Pastoor Tina,
Wuu Joanne,
Mufson Elliott J.,
Ikonomovic Milos D.
Publication year - 2006
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.2006.05.1699
Subject(s) - cytisine , nicotinic agonist , cholinergic , temporal cortex , methyllycaconitine , medicine , senile plaques , alzheimer's disease , neuroscience , endocrinology , chemistry , psychology , nicotinic acetylcholine receptor , receptor , disease
null mutant mice and slices treated with anti-RAGE antibodies. Results: Abeta(1-42) at 200 nM was able to inhibit the expression of LTP after tetanic stimulation without affecting basal synaptic transmission. Remarkably, different concentrations of Abeta (1-42) were not able to inhibit LTP in slices from RAGE null mutant mice or in slices treated with blocking antibodies against RAGE. To test the hypothesis that RAGE-Abeta interaction could lead to LTP impairment trough activation of MAP-kinases, experiments were repeated in the presence of specific inhibitors. In particular, SB203580 (1microM), an inhibitor of p38 MAP-kinase, was found to rescue LTP in Abeta (1-42) treated slices. Cell culture experiments confirmed that Abeta (1-42) modulates p38 phosphorylation at [pTpY180/182] in cortical neurons. Moreover, treatment with anti-RAGE antibodies prevented changes of p38 phosphorylation by Abeta (1-42). Conclusions: Our results indicate that non-neurotoxic concentrations of Abeta (1-42) impair LTP in mouse neocortex through RAGE mediated activation of p38 MAP kinase. (Supported by NIA and Fondazione CariPisa, 05/140).