Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKIIα.

ABSTRACT: As the population ages, an increasing number of people suffer from age-related cognitive impairment. However, the mechanisms underlying this process remain unclear. Here, we found that S-nitrosoglutathione reductase (GSNOR), the key enzyme that metabolizes intracellular nitric oxide (NO) and regulates S-nitrosation, was significantly increased in the hippocampus of both aging humans and mice. Transgenic mice overexpressing GSNOR exclusively in neurons showed cognitive impairment in behavioral tests, including the Morris water maze, fear conditioning, and the Y-maze test. We also found that GSNOR transgenic mice have LTP defects and lower dendrite spine density, whereas GSNOR knock-out mice rescued the age-related cognitive impairment. Analysis of S-nitrosation showed signific

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6596611 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature