Lycium barbarum polysaccharide ameliorates corticosterone-induced cognition decline with modulation of CRHR1

Lycium barbarum polysaccharide (LBP) has anti-inflammatory, anti-oxidation and anti-aging properties, but the mechanism of LBP on stress-induced cognitive dysfunction caused by elevated GC level is still unclear. Therefore, the present study aimed to investigate the mechanism of LBP on corticosterone-injected（CORT-injected） cognitive impairment. The rat model was induced by corticosterone in vivo. Water maze test and HE staining were used to observe the effect of LBP on cognitive function and brain morphology in CORT-injected rats. RT-qPCR, Western blot, and immunofluorescence were used to detect the expression of proteins. SH-SY5Y cells were treated with CORT and D-gal in vitro, respectively. The effect of LBP on cell proliferation was observed, and western blotting was detected in the protein expressions. In this study, LBP treatment ameliorated CORT-induced learning and cognitive function and protected hypothalamic and hippocampal neurons from injury in vivo. In addition, LBP reduced plasma corticosterone concentrations in CORT-injected rats. The results also indicated that LBP enhanced the expression of synapsis-related proteins PSD95 and SYN by up-regulating the expression of CRHR1 and RGS2 in the hippocampus and hypothalamus of the model group. Meanwhile, we confirmed that LBP enhanced CORT - and D-Gal-induced proliferation of SH-SY5Y cells in vitro, and further verified the expression changes of CRHR1, RGS2, and synapse-related proteins. This study demonstrates that LBP ameliorated CORT-induced cognition decline by regulating CRHR1. Therefore, LBP may represent a potential drug for the prevention of cognition dysfunction in patients caused by increased GCs.