Improvement of depression-like behaviors and neuroinflammation in adolescent depressed mice using Maresin-1

Abstract:

Objective To elucidate the effect of Maresin-1（MaR1） on chronic social defeated stress（CSDS）-induced depression-like behaviors in adolescent mice（5-8 weeks old），validate its role in CSDS-induced neuroinflammation，and provide a reference for understanding the molecular mechanisms of depression and exploring biomarkers.Methods Multiple methods were used to measure depression-like behaviors and neuroinflammation in C57BL/6J mice ten days after CSDS induction. The mice were treated with MaR1（5 μg/kg） intravenously every two days to observe its effect on CSDS-induced depression-like behaviors and neuroinflammation. Behavioral experiments were followed by positron emission tomography-computerized tomography（PET-CT） scanning and quantitative analysis of PET images. The mouse brain tissue samples were collected for immunofluorescence staining，and the immunofluorescence intensities of Iba-1 cells in the hippocampal region and translocator protein（TSPO） were calculated using Image J. The mouse hippocampus was dissected on ice，immediately frozen in liquid nitrogen，and stored at -80°C for subsequent RNA extraction. A kit was used to measure the levels of tumor necrosis factor-α（TNF-α），interleukin-1 beta（IL-1β），and IL-4.Results Compared to the control group，mice subjected to CSDS stress showed a lower sucrose preference ratio（P=0.003），lower social interaction ratio（P=0.000），longer immobility time（P=0.002），and microglial cell activation in the hippocampal region evidenced by increased standardized uptake values（P=0.020），enhanced immunofluorescence intensity of Iba-1 and TSPO（P=0.000），and increased proinflammatory cytokines IL-1β and TNF-α（P=0.016，0.036）. In contrast，MaR1 improved CSDS-induced depression-like behaviors，inhibited microglia activation，and reduced the expression of proinflammatory factors.Conclusion MaR1 can alleviate CSDS-induced depression-like behaviors in adolescent mice and inhibit the activation of microglia. Neuroinflammation is a potential pathogenic factor for depression in adolescents，and drugs with anti-inflammatory properties such as MaR1 hold promise for use as a clinically relevant antidepressant，which needs further investigation.