AUTHOR=Wang Chen , Zhu Ming-Hao , Sun Na , Shen Wei , Jiang Ning , Zhao Qin-Shi , Zhang Yong-Xiang , Huang Yan , Zhou Wen-Xia 

TITLE=Isorhynchophylline ameliorates stress-induced emotional disorder and cognitive impairment with modulation of NMDA receptors

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 16 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.1071068

DOI=10.3389/fnins.2022.1071068

ISSN=1662-453X

ABSTRACT=Isorhynchophylline is one of the main active ingredients from Uncaria rhynchophylla, the effects and mechanisms of isorhynchophylline on stress-induced emotional disorder and cognitive impairment remains unclear. In this study, we found that isorhynchophylline could improve corticosterone-induced in vivo long-term potentiation (LTP) impairment significantly, indicating positive effects on stress. Therefore, 28-days chronic unpredictable mild stress (CUMS) model was adopted to evaluate the anti-stress effects of isorhynchophylline. The results showed that isorhynchophylline improved CUMS-induced weight loss, anxiety- and depression-like behavior, and spatial memory impairment. Isorhynchophylline reduced CUMS-induced corticosterone elevation. Meanwhile, glutamate and the expression of N-methyl-D-aspartic acid (NMDA) receptor (GluN2A and GluN2B), which play an important role in the process of emotion and memory, were increased in the CUMS mice, while D-serine and the expression of serine racemase (SR) decreased significantly, and isorhynchophylline could restore these changes to normal level. These results indicated that isorhynchophylline could ameliorate stress-induced emotional disorder and cognitive impairment, modulating NMDA receptors might be one of the underlying mechanisms.