Effects of an inhibitor of alpha-secretase, which metabolizes the amyloid peptide precursor, on memory formation in rats.
Intracortical administration of 10(-4) M batimastat, a specific inhibitor of alpha-secretase (a metalloproteinase which cleaves the amyloid peptide precursor), decreased the number of correct runs in a single-level eight-arm maze to 92.78 +/- 1.03% compared with baseline (p < 0.01) within 60 min. However, injection of batimastat into the cerebral cortex of animals during the early postnatal period (days 5 and 7 of life) led to impaired orientation in the simple single-level maze when these adults reached adulthood (90.92 +/- 2.21% correct runs, p < 0.001) as compared with controls. The data obtained here provide evidence for the important role of alpha-secretase in memory processes. The possible role of alpha-secretase in memory processes and the pathogenesis of Alzheimer's disease is discussed.
Dubrovskaya
N M
NM
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Nalivaeva
N N
NN
Turner
A J
AJ
Zhuravin
I A
IA
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D053829:Amyloid Precursor Protein Secretases