Background Prenatal stress may impair the connection between central nervous system during offspring development, and the CX3CL1/CX3CR1 axis establishes a unique communication system between neurons and microglia.

Objective To clarify whether prenatal stress has an impact on the CX3CL1/ CX3CR1 axis in impairing offspring cognitive function and explore its mechanism of action.

Methods Twelve pregnant SD rats were randomly divided into prenatal stress group and control group, with 6 rats in each group. The prenatal stress group was subjected to restrictive stress on the 15th to 21st day of pregnancy, while the control group was fed normally. ELISA was used to detect plasma glucocorticoids in maternal and offspring peripheral blood, and cognitive function in adult offspring was evaluated using four behavioral methods: open field, elevated cross maze, new object recognition, and Y-maze. Immunofluorescence staining and Western blot were used to detect the expression of CX3CL1, CX3CR1, and Iba-1.

Results The prenatal stress group and its offspring had elevated levels of glucocorticoids (P＜0.05). In the open field experiment, the offspring of the prenatal stress group showed a significant decrease in the central area retention time compared to the control group (P＜0.05), and a significant decrease in the number and retention time of entering the open arm in the elevated cross maze compared to the control group (P＜0.05), indicating anxiety like behavior. In the recognition of new objects, the recognition index significantly decreased (P＜0.05), indicating a decrease in learning and memory abilities. In the Y-maze, the recognition of new arms was significantly reduced (P＜0.05), indicating a decrease in spatial memory abilities, and increased expression of Iba-1 (P＜0.05), CX3CR1 (P＜0.05), and CX3CL1 (P＜0.05) activated by prenatal stress in offspring microglia during pregnancy.

Conclusion Prenatal stress damage to cognitive function in adult offspring may be related to CX3CL1/CX3CR1 communication disorders.