Vaccination with peptide 173-193 of acetylcholine receptor α7-subunit prevents memory loss in olfactory bulbectomized mice

J Alzheimers Dis. 2010;21(1):249-61. doi: 10.3233/JAD-2010-091474.

Abstract

We studied the ability of four non-conjugated alpha7-subunit fragments of the nicotinic acetylcholine receptor to induce an immune response and to protect memory in olfactory bulbectomized mice which demonstrate abnormalities similar to Alzheimer's disease (AD). Vaccination only with the alpha7-subunit fragment 173-193 was shown to rescue spatial memory, to restore the level of alpha7 acetylcholine receptors in the cortex, and to prevent an increase in the amyloid-beta (Abeta) level in brain tissue in these animals. Antibodies against the peptide 173-193 were revealed in blood serum and cerebrospinal liquid in the bulbectomized mice. Passive immunization with mouse blood sera containing antibodies to the peptide 173-193 also restored memory in bulbectomized animals. The observed positive effect of both active and passive immunization with the fragment of alpha7-subunit on memory of bulbectomized mice provides a new insight into an anti-AD drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Analysis of Variance
  • Animals
  • Antibodies / pharmacology
  • Antibodies / therapeutic use
  • Behavior, Animal
  • Bungarotoxins / metabolism
  • Dose-Response Relationship, Immunologic
  • Immunotherapy, Active / methods*
  • Iodine Isotopes / metabolism
  • Male
  • Maze Learning / physiology
  • Memory Disorders / etiology
  • Memory Disorders / immunology*
  • Memory Disorders / metabolism
  • Memory Disorders / prevention & control*
  • Mice
  • Olfaction Disorders / complications
  • Olfaction Disorders / etiology
  • Olfactory Bulb / surgery
  • Peptides / immunology*
  • Protein Binding / immunology
  • Protein Binding / physiology
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / immunology
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Amyloid beta-Peptides
  • Antibodies
  • Bungarotoxins
  • Chrna7 protein, mouse
  • Iodine Isotopes
  • Peptides
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor