The neurochemical and behavioral effects of beta-amyloid peptide(25-35)

Beta-amyloid protein (A beta) fragments have been shown to be neurotoxic and/or enhance neuronal vulnerability when injected into the hippocampus. We investigated alterations in monoamine contents, including norepinephrine (NE), 5-HT and dopamine (DA) in the rat locus coeruleus (LC) one week following the injection of beta-amyloid peptide fragment 25-35 (beta (25-35)) into the left dorsal hippocampal areas CA1-3. A single treatment of beta (25-35) had no effect on any monoamine levels. Rats that received two treatments (separated by 7 days) revealed significant elevations in NE, 5-HT, and 5-HIAA as compared with the control group injected with ddH2O. However, these changes were observed in the LC on the contralateral side, whereas the injected side exhibited no significant change. These effects may result from an enhanced synthesis of NE by the contralateral LC neurons to compensate for the loss of tyrosine hydroxylase and accompanying recurrent inhibition in a small number of their population. In a second experiment, the influence of beta (25-35) on spatial learning was evaluated using a Morris water maze task. Rats received bilateral injections of beta (25-35) into hippocampal areas CA1-3. The results indicate that beta (25-35)-treated rats exhibited significantly longer latencies and swim distances to locate the submerged platform than did members of the control group.