TY - JOUR

T1 - Prolonged Aggressive Experience Accelerates Resolution of Inflammation in Blood and Microglia After Repeated LPS Treatment

AU - Mutovina, Anastasia

AU - Sapronova, Anna

AU - Ayriyants, Kseniya

AU - Ryabushkina, Yulia

AU - Khantakova, Julia

AU - Межевалова, Полина Сергеевна

AU - Ritter, Polina

AU - Bondar, Natalya

N1 - Mutovina, A.; Sapronova, A.; Ayriyants, K.; Ryabushkina, Y.; Khantakova, J.; Mezhevalova, P.; Ritter, P.; Bondar, N. Prolonged Aggressive Experience Accelerates Resolution of Inflammation in Blood and Microglia After Repeated LPS Treatment. Int. J. Mol. Sci. 2025, 26, 12007. https://doi.org/10.3390/ijms262412007 The study was supported by funding of the Russian Science Foundation (№ 24-25-00189).

PY - 2025/12/13

Y1 - 2025/12/13

N2 - This study investigated how prolonged aggression in male CD1 mice alters responses to chronic LPS (lipopolysaccharide)-induced inflammation. Experience of aggression induced pathological aggression in 36% of mice. Following LPS, aggressors resolved systemic inflammation within five days—evidenced by normalized locomotor activity, WBC (white blood cells), and lymphocyte counts—while controls remained inflamed. LPS did not alter established aggression or anxiety. Furthermore, aggressors demonstrated accelerated inflammation resolution in the brain, showing a higher proportion of resting microglia and a lower percentage of activated microglia following LPS-induced inflammation compared to control animals. Gene expression analysis revealed a more pronounced inflammatory response in the hypothalamus than in the nucleus accumbens. Aggressive mice exhibited a profile associated with inflammation resolution, indicated by increased expression of the Trem2 gene. These differential immune responses may be modulated by the dopaminergic system. Elevated Drd1 gene expression in the hypothalamus could possibly contribute to the anti-inflammatory signaling, while changes in nucleus accumbens dopaminergic activity, involving D2 receptor activation, appear linked to the development of pathological aggression. Thus, this study demonstrates that prolonged aggression induces persistent changes in behavioral, neuroimmune, and neuroendocrine systems in male CD1 mice. Aggressive animals develop a distinct neuroimmune phenotype characterized by accelerated resolution of both systemic and brain inflammation following LPS challenge.

AB - This study investigated how prolonged aggression in male CD1 mice alters responses to chronic LPS (lipopolysaccharide)-induced inflammation. Experience of aggression induced pathological aggression in 36% of mice. Following LPS, aggressors resolved systemic inflammation within five days—evidenced by normalized locomotor activity, WBC (white blood cells), and lymphocyte counts—while controls remained inflamed. LPS did not alter established aggression or anxiety. Furthermore, aggressors demonstrated accelerated inflammation resolution in the brain, showing a higher proportion of resting microglia and a lower percentage of activated microglia following LPS-induced inflammation compared to control animals. Gene expression analysis revealed a more pronounced inflammatory response in the hypothalamus than in the nucleus accumbens. Aggressive mice exhibited a profile associated with inflammation resolution, indicated by increased expression of the Trem2 gene. These differential immune responses may be modulated by the dopaminergic system. Elevated Drd1 gene expression in the hypothalamus could possibly contribute to the anti-inflammatory signaling, while changes in nucleus accumbens dopaminergic activity, involving D2 receptor activation, appear linked to the development of pathological aggression. Thus, this study demonstrates that prolonged aggression induces persistent changes in behavioral, neuroimmune, and neuroendocrine systems in male CD1 mice. Aggressive animals develop a distinct neuroimmune phenotype characterized by accelerated resolution of both systemic and brain inflammation following LPS challenge.

KW - pathological aggression

KW - neuroinflammation

KW - LPS

KW - microglia

KW - dopamine

KW - hypothalamus

KW - nucleus accumbens

UR - https://www.scopus.com/pages/publications/105025821638

M3 - Article

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 24

M1 - 12007

ER -