Morin Improves Cognitive Deficits in an in Vivo Model of Vascular Dementia by Modulating the N-methyl-D-aspartate Receptor Signaling Pathways.

Abstract

The research on the pathoetiology of vascular dementia (VaD) highlights a notable deficiency in effective therapies within present medical practices. Morin exhibits promising therapeutic benefits due to its strong antioxidant and anti-inflammatory properties. However, its specific functions and mechanisms in VaD require further elucidation. In this study, VaD animals were established by permanent bilateral common carotid artery occlusion (2VO). Cognitive functions and behavioral analysis were performed in rats. Moreover, the state of oxidative stress, inflammation, and apoptosis was evaluated. Western blotting and ELISA were performed to investigate synaptic plasticity-related proteins, such as SYP, PSD-95, and NMDA receptor proteins (NR1, NR2A, NR2B). The results revealed that morin reduced oxidative stress in the hippocampus by lowering MDA and recombinant reactive oxygen species modulator 1 (Romo-1) levels, while simultaneously enhancing the activities of SOD and GPx. In addition, morin increased the levels of anti-inflammatory cytokines (IL-10 and IL-4), while reducing the levels of pro-inflammatory cytokines (IL-1β and IL-6), and suppressed apoptosis through downregulation of caspase 3 and upregulation of BCL-2. Additionally, morin promoted the expression of PSD95, SYP, and NMDAR proteins in animals with VaD. The obtained data suggest that morin is associated with improved cognitive impairments in VaD rats, which may be mediated by the reduction of apoptosis, oxidative stress, and inflammation in the hippocampus, as well as by restoring the signaling of NMDARs.