Repeated intracerebroventricular administration of β-amyloid25–35 to rats decreases muscarinic receptors in cerebral cortex

Abstract

The effects of repeated in vivo administration to rats of β-amyloid25–35 (βA25–35) on several cholinergic markers have been studied and compared with those of a peptide with a scrambled sequence. Rats received intracerebroventricular injections of βA25–35 (5 or 20 μg/day) for 7 days and they were sacrificed at 2 or 3 weeks survival. The density of total muscarinic receptors labeled with [3H]N-methyl-scopolamine was dose-dependently decreased by βA25–35 in the cerebral cortex at 3 weeks survival. No changes were observed at 2 weeks survival in cerebral cortex or in the hippocampus, at any time. βA25–35 administration did not modify choline acetyltranferase activity in cerebral cortex. However, in βA25–35-treated rats hypertrophic/hyperactive positive acetylcholinesterase nucleus basalis cholinergic neurons were observed at 2 weeks survival, while the density of acetylcholinesterase-positive fibers of cerebral cortex was increased along with the number of cortical positive neurons at 3 weeks survival. These results suggest that increased cholinergic function may be responsible of muscarinic receptor down-regulation. Given the involvement of cholinergic systems in memory and learning, repeated administration of βA25–35 may represent a good approach to explore the role of βA in Alzheimer's disease and to develop therapeutic strategies relevant to it.