Abstract: BACKGROUND: Stress-induced damage to hippocampal neurons may underlie abnormalities in neuronal structure and function, ultimately leading to mood disorders. G protein-coupled receptors in brain tissue play an important role in mood regulation.
OBJECTIVE: To analyze the mechanism of depression-like behavior in chronic social defeat stress mice based on high-throughput sequencing and bioinformatics analysis. 
METHODS: C57BL/6J mice were randomly divided into control group and model group. There was no special treatment in the control group, while a mouse model of chronic social defeat stress was established in the model group. Depression-like behavior was assessed through the sucrose preference test, tail suspension test, and forced swim test. Anxiety behavior was evaluated using the elevated plus-maze, while social behavior was measured through the social interaction test. Cognitive function was assessed with the Y-maze spontaneous alternation test. Immunofluorescence staining was performed to quantify microglia markers in the mouse hippocampus, and Nissl staining was used to examine neuronal damage in mice. High-throughput sequencing was used to identify differentially expressed genes and gene enrichment in the mouse hippocampus, and qPCR was used to measure the expression of G protein-coupled receptors in the mouse hippocampus.
RESULTS AND CONCLUSION: (1) Compared with the control group, chronic social defeat stress mice showed significant behavioral impairments, including increased anxiety, depression, and cognitive deficits. (2) Additionally, the Nissl body light density in hippocampal neurons was significantly reduced in chronic social defeat stress mice. (3) Sequencing results revealed synaptic damage in the neurons after chronic social defeat stress. Microglia activation was also markedly increased in the hippocampus of CSDS mice. Furthermore, the expression of G protein-coupled receptors in the hippocampus was significantly higher in chronic social defeat stress mice compared with the control group. These findings suggest that chronic social defeat stress induces anxiety, depression, and cognitive deficits in mice, accompanied by neuropathological changes in the hippocampus, and that altered G protein-coupled receptors expression may play a key role in these behavioral and neuropathological changes.

Key words: chronic social defeat stress, depression, anxiety, hippocampus, GPRs, neurons, synapse, inflammation, cognition