Effects of NMDAR2B-mediated Hippocampal Neuron Protection on Cognitive Function in Rats with Depression

Background To observe the changes in cognitive function of depressive model rats after fluoxetine intervention, and further explore the correlation between fluoxetine's influence on cognitive function in depressive model rats and the N-methyl-D-aspartate receptor 2B subunit (NMDAR2B) in the hippocampus, as well as its impact on hippocampal neurons. Methods The depression model was established using Chronic Unpredictable Mild Stress (CUMS) combined with solitary confinement, followed by fluoxetine intervention upon successful establishment. Neurobehavioral assessments were conducted to evaluate the rats' emotions, cognition, and learning abilities. Molecular docking technology was employed to observe the affinity between fluoxetine and the NMDAR2B subunit. Proteomic analysis was performed to detect changes in NMDAR2B protein, and histopathological staining was used to observe pathological alterations in neurons in the rat hippocampus. Finally, statistical analysis of the data was conducted. Results After modeling, the rats exhibited depressive-like behaviors, impaired cognitive learning and memory abilities, significantly reduced expression and concentration of NMDAR2B protein, pathological damage to neurons in the hippocampus, decreased number of Nissl bodies, markedly reduced dendritic spine density, damaged synaptic structures with decreased synaptic vesicles. Following fluoxetine intervention, these conditions showed varying degrees of recovery. Correlation analysis revealed that the cognitive and learning abilities of rats were impaired, accompanied by a significant decrease in dendritic spine density and a decline in the expression of the NMDAR2B protein. Conclusions Fluoxetine may exert neuroprotective effects by regulating the expression of NMDAR2B protein in the hippocampus, thereby improving the cognitive function of depressed rats.