Serum Metabolomics and Bio-Network Analysis Reveal the Biological Mechanism of Aggressive Behavior in CD-1 Retired Breeder Mice
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Modern Research Center for Traditional Chinese Medicine, Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Shanxi University, Taiyuan 030006, China

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Q955

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    Abstract:

    [Objectives] Aggressive behavior represents a prevalent manifestation of mental disorders, with severe violence posing detrimental consequences for the society. During the screening of CD-1 retired breeder mice, we found significant differences in aggression among individuals, and selecting those with higher aggression is crucial for successfully establishing the model of depression induced by chronic social defeat stress (CSDS). Therefore, this study investigates the metabolic pathways and related genes in CD-1 retired breeder mice during aggressive behavior, aiming to reveal the mechanisms of aggressive behavior. [Methods] During the screening phase of aggressive mice of the CSDS-induced depression model, CD-1 retired breeder mice were housed in individual cages for a week to establish territorial awareness, and then attack and non-attack mice were screened out through the resident-intruder test. Compound Discoverer 3.0 was used for serum metabolomics based on ultra performance liquid chromatography-tandem mass spectrometry to identify differential metabolites and metabolic pathways between the attack group and the non-attack group of mice. Meanwhile, biological network analysis based on Cytoscape 3.9.1 software was performed to identify key metabolic pathways and genes involved in the occurrence of aggressive behavior. Independent samples t-test was performed to compare the aggressive behavior between the two groups. [Results] The serum metabolomics (Appendix 1) screened out 12 differential metabolites between the attack group and non-attack group of CD-1 retired breeder mice. Among them, DL-glutamic acid, N-acetyl-L-leucine, dehydroascorbic acid, oleamide, trans-palmitoleate, choline, and linoleamide were significantly increased, while tetradecanoylcarnitine, cholic acid, 1-acyl-sn-glycero-3-phosphocholine, sn-glycero-3-phosphoethanolamine, and octadecanoic acid were significantly decreased (P < 0.05). The results above, combined with those of biological network analysis (Figs. 5, 6 and Table 3), show that glycerophospholipid metabolism is a key pathway for aggressive behavior and Pld1, Pld2, Pla2g5, Pla2g3, Pla2g10, Lypla1, Lcat, Chka, and Chat in the metabolic pathway may be key genes shared by aggressive behavior and differential metabolites (Table 4). [Conclusion] The occurrence of aggressive behavior may be closely related to glycerophospholipid metabolism, which is not only significant for elucidating the metabolome of aggressive behavior in CD-1 retired breeder mice but also of great value for the scientific research and standardization of the model of CSDS-induced depression.

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HU Ting, WANG Qi, ZHAO Yun-Hao, LI Kai-Wen, WANG Yu-Jing, QIN Xue-Mei, TIAN Jun-Sheng. 2025. Serum Metabolomics and Bio-Network Analysis Reveal the Biological Mechanism of Aggressive Behavior in CD-1 Retired Breeder Mice. Chinese Journal of Zoology, 60(5): 702-719.

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  • Received:November 22,2024
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  • Online: October 21,2025
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