P2–064: Long–term cognitive and behavioral response, and liquid crystalline states of brain mitochondrial membrane in estrogen–treated mice exposed to low–dose radiation In utero

nAChRs and partially blocks the action of ACh on 7 nAChRs (Grassi et al., 2003; Pettit et al., 2001; Wang et al., 2000). The nature of the link between amyloid peptides, nAChRs and AD pathology is yet to be established. Objective(s): Determine the actions of Dutch, Swedish and Flemish variants of A on recombinant nicotinic acetylcholine receptors. Methods: We used two-electrode voltage-clamp to study the effects of the Swedish, Dutch and Flemish mutant forms of A 1-42 (10 nM) on the ACh-evoked responses of recombinant human 7, 4 2 and 3 4 nAChRs expressed in Xenopus oocytes. Results: We found that the Swedish peptide acted as a non-competitive antagonist of human 7 nAChRs and an allosteric enhancer of ACh-evoked currents mediated by 4 2 nAChRs, but had no effect on 3 4 nAChRs. These actions are identical to the actions of wild type A 1-42 on these human neuronal nicotinic receptors (Pym et al., 2005). In contrast to this, both the Flemish and Dutch mutant forms of A 1-42 caused an enhancement of ACh-evoked currents in all neuronal nicotinic receptors tested. Conclusions: This is the first demonstration that these mutations in A have specific actions on nAChRs. These results may have implications for the subtle differences in the pathology of familial AD when compared to sporadic AD and highlights the sensitivity of nAChR subtypes to variants of A 1-42.