[Changes in the activity of amyloid-degrading metallopeptidases leads to disruption of memory in rats].

In old male Wistar rats (older than 12 months), or adult males (3-4 months) subjected to prenatal hypoxia (7% 02, 3 h, E14), a disruption of short-term memory was observed. The prenatal hypoxia also led to a decrease in the brain cortex expression of metallopeptidases neprilysin (NEP) and endothelin-converting enzyme (ECE-1) which regulate some neuropeptides and are the main beta-amyloid-degrading enzymes. Moreover, a significant decrease (by 2.7 times) in NEP activity in the sensorimotor cortex of old and adult rats subjected to prenatal hypoxia (by 1.7 times) was observed. To confirm possible involvement of these enzymes in memory, the analysis of the effect of microinjections of phosphoramidon (an inhibitor of NEP and ECE-1), and thiorphan (an inhibitor of NEP) into the rat sensorimotor cortex was carried out. In a two-level radial maze test, a disruption of short-term memory was observed 60 and 120 min after i.c. injection ofphosphoramidon (5.9 microg/microl) and 30 and 60 min after i.c. injection of thiorphan (2.5 microg/microl). The involvement of NEP and ECE-1 in short-term memory suggests that a decrease in the level of expression and activity of metallopeptidases involved in metabolism of beta-amyloid peptide (Abeta) and other neuropeptides is one of the main factors in disruption of cognitive functions after prenatal hypoxia or in the process of ageing.