Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia.

Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia. Neurochem Res. 2019 Apr 20;: Authors: Zhuravin IA, Dubrovskaya NM, Vasilev DS, Kozlova DI, Kochkina EG, Tumanova NL, Nalivaeva NN Abstract The amyloid-degrading enzyme neprilysin (NEP) is one of the therapeutic targets in prevention and treatment of Alzheimer's disease (AD). As we have shown previously NEP expression in rat parietal cortex (Cx) and hippocampus (Hip) decreases with age and is also significantly reduced after prenatal hypoxia. Following the paradigms for enhancement of NEP expression and activity developed in cell culture, we analysed the efficacy of various compounds able to upregulate NEP using our model of prenatal hypoxia in rats. In addition to the previous data demonstrating that valproic acid can upregulate NEP expression both in neuroblastoma cells and in rat Cx and Hip we have further confirmed that caspase inhibitors can also restore NEP expression in rat Cx reduced after prenatal hypoxia. Here we also report that administration of a green tea catechin epigallocatechin-3-gallate (EGCG) to adult rats subjected to prenatal hypoxia increased NEP activity in blood plasma, Cx and Hip as well as improved memory performance in the 8-arm maze and novel object recognition tests. Moreover, EGCG administration led to an increased number of dendritic spines in the hippocampal CA1 area which correlated with memory enhancement. The da...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research