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

AuthorsPavía, J.; Alberch, J.; Álvarez-González, Isabel ; Toledano Gasca, Adolfo ; Ceballos, María L. de
Issue Date2000
CitationNeuroscience Letters 278: 69- 72 (2000)
AbstractThe 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.
Identifiersdoi: 10.1016/S0304-3940(99)00900-3
issn: 0304-3940
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