Repeated intracerebroventricular administration of beta-amyloid(25-35) to rats decreases muscarinic receptors in cerebral cortex

Neurosci Lett. 2000 Jan 7;278(1-2):69-72. doi: 10.1016/s0304-3940(99)00900-3.

Abstract

The effects of repeated in vivo administration to rats of beta-amyloid(25-35) (betaA(25-35)) on several cholinergic markers have been studied and compared with those of a peptide with a scrambled sequence. Rats received intracerebroventricular injections of betaA(25-35) (5 or 20 microg/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 betaA(25-35) 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. BetaA(25-35) administration did not modify choline acetyltranferase activity in cerebral cortex. However, in betaA(25-35)-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 betaA(25-35) may represent a good approach to explore the role of betaA in Alzheimer's disease and to develop therapeutic strategies relevant to it.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / analysis
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Basal Nucleus of Meynert / drug effects
  • Basal Nucleus of Meynert / metabolism
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Choline O-Acetyltransferase / analysis
  • Cholinergic Fibers / drug effects
  • Down-Regulation / drug effects*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / genetics
  • Neuronal Plasticity / drug effects
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / genetics
  • Receptors, Presynaptic / drug effects

Substances

  • Amyloid beta-Peptides
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Receptors, Muscarinic
  • Receptors, Presynaptic
  • amyloid beta-protein (25-35)
  • Choline O-Acetyltransferase
  • Acetylcholinesterase