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We investigated the signal transduction consequences of exposure to nanomolar to low micromolar concentrations of aggregate forms of \u03b2\u2010amyloid in the hippocampus. We found that, in addition to activation of ERK MAPK and its downstream target ribosomal S6 kinase in hippocampal slice cultures following acute exposure to oligomeric \u03b2\u2010amyloid<jats:sub>1\u221242<\/jats:sub>, ERK activation also requires phosphoinositide\u20103 kinase activity. These effects were contingent on the \u03b17 subtype of nicotinic acetylcholine receptor. Hippocampal slice cultures treated acutely with oligomeric \u03b2\u2010amyloid<jats:sub>1\u221242<\/jats:sub> did not exhibit JNK MAPK activation; however, chronic exposure to oligomers or high molecular weight aggregates of \u03b2\u2010amyloid<jats:sub>1\u221242<\/jats:sub> led to JNK MAPK activation coincident with ERK MAPK down\u2010regulation. In contrast to the effects of acute application of oligomeric \u03b2\u2010amyloid<jats:sub>1\u221242<\/jats:sub>, nicotine activated ERK MAPK via \u03b17 nicotinic acetylcholine receptors utilizing protein kinase A as an intermediate. In conclusion, we found that both the physical state and duration of exposure to \u03b2\u2010amyloid are determinants of MAPK recruitment in hippocampus. We also found that nicotine and \u03b2\u2010amyloid activate ERK MAPK via \u03b17 nicotinic acetylcholine receptors but use distinct intermediate kinases. These data indicate the existence of differential coupling of \u03b17 to downstream targets depending on the type of ligand that leads to receptor activation.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02722.x","type":"journal-article","created":{"date-parts":[[2004,9,24]],"date-time":"2004-09-24T12:55:31Z","timestamp":1096030531000},"page":"349-361","source":"Crossref","is-referenced-by-count":85,"title":["MAPK recruitment by \u03b2\u2010amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time"],"prefix":"10.1111","volume":"91","author":[{"given":"Karen A.","family":"Bell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"O'Riordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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