Vasilev Dimitrii S, Dubrovskaya Nadezhda M, Zhuravin Igor A, Nalivaeva Natalia N
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS, 44 Thorez Avenue, Saint Petersburg, 194223, Russia.
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
J Mol Neurosci. 2021 Sep;71(9):1772-1785. doi: 10.1007/s12031-020-01786-3. Epub 2021 Jan 12.
A neuropeptidase, neprilysin (NEP), is a major amyloid (Aβ)-degrading enzyme involved in the pathogenesis of Alzheimer's disease (AD). The olfactory system is affected early in AD with characteristic Aβ accumulation, but data on the dynamics of NEP expression in the olfactory system are absent. Our study demonstrates that NEP mRNA expression in rat olfactory bulbs (OB), entorhinal cortex (ECx), hippocampus (Hip), parietal cortex (PCx) and striatum (Str) increases during the first postnatal month being the highest in the OB and Str. By 3 months, NEP mRNA levels sharply decrease in the ECx, Hip and PCx and by 9 months in the OB, but not in the Str, which correlates with declining olfaction in aged rats tested in the food search paradigm. One-month-old rats subjected to prenatal hypoxia on E14 had lower NEP mRNA levels in the ECx, Hip and PCx (but not in the OB and Str) compared with the control offspring and demonstrated impaired olfaction in the odour preference and food search paradigms. Administration to these rats of a histone deacetylase inhibitor, sodium valproate, restored NEP expression in the ECx, Hip and PCx and improved olfaction. Our data support NEP involvement in olfactory function.
一种神经肽酶，中性内肽酶（NEP），是参与阿尔茨海默病（AD）发病机制的主要淀粉样蛋白（Aβ）降解酶。嗅觉系统在AD早期就受到影响，伴有特征性的Aβ积累，但关于嗅觉系统中NEP表达动态的数据却缺失。我们的研究表明，大鼠嗅球（OB）、内嗅皮质（ECx）、海马体（Hip）、顶叶皮质（PCx）和纹状体（Str）中的NEP mRNA表达在出生后的第一个月内增加，在OB和Str中最高。到3个月时，ECx、Hip和PCx中的NEP mRNA水平急剧下降，到9个月时OB中的NEP mRNA水平下降，但Str中的没有下降，这与在食物搜索范式中测试的老年大鼠嗅觉下降相关。与对照后代相比，在胚胎第14天接受产前缺氧的1月龄大鼠在ECx、Hip和PCx中NEP mRNA水平较低（但在OB和Str中没有），并且在气味偏好和食物搜索范式中表现出嗅觉受损。给这些大鼠施用组蛋白脱乙酰酶抑制剂丙戊酸钠可恢复ECx、Hip和PCx中的NEP表达并改善嗅觉。我们的数据支持NEP参与嗅觉功能。
