We found that CUMS induced depressive-like behaviors including decreased sucrose preference ratio, prolonged immobility and reduced locomotor and exploratory activity; cognitive deficits including spatial learning and memory impairment; reduced dendritic spine density and number of branches; thinned postsynaptic density; downregulated SIRT1/microRNA-134 pathway, decreased BDNF and synaptic proteins including synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) expression in the hippocampus.
We found that the oral pretreatment of glycyrrhizin inhibited HMGB1 cytosolic expression, increased the PSD-95 protein expression, and attenuated the severity of postoperative memory impairment, as indicated by the shorter swimming latency and distance in MWM trials when compared with the mice subjected to the surgery alone.
Therefore, our study suggests that CREB and PSD95 are novel substrates of PERK, so inhibition of PERK phosphorylation using GSK2656157 would be beneficial against memory impairment after TBI.