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

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2019 Apr 22

PMID 31006092

Citations 12

Authors

I A Zhuravin

N M Dubrovskaya

D S Vasilev

D I Kozlova

E G Kochkina

N L Tumanova

N N Nalivaeva

Affiliations

Soon will be listed here.

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 data obtained allowed us to conclude that the decrease in the activity of the amyloid-degrading enzyme NEP, as well as a reduction in the number of labile interneuronal contacts in the hippocampus, contribute to early cognitive deficits caused by prenatal hypoxia and that there are therapeutic avenues to restore these deficits via NEP activation which could also be used for designing preventive strategies in AD.

Citing Articles

Valproate Administration to Adult 5xFAD Mice Upregulates Expression of Neprilysin and Improves Olfaction and Memory.

Vasilev D, Dubrovskaya N, Tumanova N, Tursunov A, Nalivaeva N J Mol Neurosci. 2024; 74(4):110.

PMID: 39549146 DOI: 10.1007/s12031-024-02287-3.

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.

Cui C, Jiang X, Wang Y, Li C, Lin Z, Wei Y Cell Mol Neurobiol. 2024; 44(1):58.

PMID: 39105862 PMC: 11303443. DOI: 10.1007/s10571-024-01491-4.

YTHDF3 modulates the Cbln1 level by recruiting BTG2 and is implicated in the impaired cognition of prenatal hypoxia offspring.

Lu L, Shi Y, Wei B, Li W, Yu X, Zhao Y iScience. 2024; 27(1):108703.

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Increased Expression of Neprilysin Is Associated with Inflammation in Preeclampsia.

Atta S, Mekky R, Ibrahim M, Abdallah M, Elbaz M, Radwan E Reprod Sci. 2023; 31(5):1385-1390.

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Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by A1-42.

Li S, Yan G, Tan Y, Xue L, Wang T, Zhao H Neural Plast. 2022; 2022:3995227.

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