[Effect of an inhibitor of alpha-secretase metabolizing amyloid precursor protein on memory in rats]

Zh Vyssh Nerv Deiat Im I P Pavlova. 2005 Nov-Dec;55(6):725-8.
[Article in Russian]

Abstract

Intracortical administration of 10(-4) M batimastat, a specific inhibitor of one of metalloproteinases metabolizing amyloid precursor protein, namely alpha-secretase, to adult rats resulted in a decrease in the number of correct runs in a one-level 8-arm maze down to 92.78 +/- 1.03% of the control values (p < 0.01) already 60 min after an injection. The effect of a single injection of the inhibitor to adult rats did not have a prolonged character. However, injections of batimastat into the cortex of brain hemispheres of rats during early postnatal ontogenesis (5th and 7th days after birth) resulted in considerable deterioration of 8-arm maze orientation of these animals at adult age (90.92 +/- 2.21% of correct runs, p < 0.001) compared to control animals. The findings suggest an important role of alpha-secretase in memorization. A possible role of alpha-secretase in memory and pathogenesis of Alzheimer's disease is discussed.

Publication types

  • English Abstract

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Endopeptidases / administration & dosage
  • Endopeptidases / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Thiophenes / pharmacology*

Substances

  • Amyloid beta-Protein Precursor
  • Protease Inhibitors
  • Thiophenes
  • Phenylalanine
  • batimastat
  • Amyloid Precursor Protein Secretases
  • Endopeptidases