Curcumin modulates oxidative stress, cortical activity and corticosterone in mice exposed to chronic social stress in the spontaneous aggressiveness model

Abstract

Abstract Stress constitutes a fundamental physiological mechanism essential for survival and environmental adaptation. Chronic social stress is a major risk factor for emotional and behavioral disturbances, including aggressiveness. Curcumin, a bioactive polyphenol derived from Curcuma longa, exhibits antioxidants, anti-inflammatory, and antidepressant properties, making it a promising neuroprotective agent. Previous studies using the Spontaneous Aggressiveness Model (MSA) demonstrated increased production of reactive oxygen species (ROS) and c-Fos expression in aggressive mice, suggesting a role for oxidative stress. This study investigated the effects of curcumin supplementation on neuroendocrine and oxidative parameters in male Swiss Webster mice subjected to chronic social stress in MSA. Animals ( n  = 60, 3 weeks old) were allocated to control and curcumin-treated groups. The treated group received a 1.5% curcumin-enriched diet for ten days before social regrouping in week 10. Behavioral categorization into non-regrouped (NR), aggressive (AgR), subordinate (Sub), and harmonious (Har) profiles were performed at week 16. Plasma corticosterone was quantified by ELISA, ROS production by DHE assay, and c-Fos expression by immunofluorescence. All procedures were approved by the Ethics Committee on Animal Use of the Oswaldo Cruz Institute (CEUA/IOC L-022/2025). Curcumin supplementation reduced attack intensity, prevented hypercortisolemia in NR mice, and decreased ROS levels in aggressive animals, supporting its antioxidant and neuroendocrine modulatory effects as a potential neuroprotective strategy under chronic social stress.