Sex-dependent effects of 56Fe irradiation on contextual fear conditioning in C57BL/6J mice

Abstract

Effects of irradiation on hippocampal function have been mostly studied in male rodents and relatively little is known about potential effects of irradiation on hippocampal function in female rodents. Moreover, although the long-term effects of clinical radiation on cognitive function have been well established, the effects of other forms of irradiation, such as high charged, high energy radiation (HZE particles) that astronauts encounter during space missions have not been well characterized. In this study we compared the effects of (56)Fe irradiation on fear conditioning in C57BL/6J female and male mice. Hippocampus-dependent contextual fear conditioning was impaired in female mice but improved in male mice following (56)Fe irradiation. Such impairment was not seen for hippocampus-independent cued fear conditioning. Thus, the effects of (56)Fe irradiation on hippocampus-dependent contextual fear conditioning are critically modulated by sex.

FIGURE 1

Locomotor activity (A) and anxiety-like behavior (B) in the open field test are not altered by ⁵⁶Fe irradiation; however females (N = 29) moved more than males (N = 28) (**P < 0.01). (C) 3Gy irradiated females and 2Gy irradiated males did not show novel object recognition (P > 0.05, novel object vs. the two familiar objects, PLSD); however, all other groups of mice did explored the novel object more than the two familiar ones (*P < 0.05). (D) Diagram of the fear conditioning paradigm. (E and F) Males showed more contextual and cued freezing than females in the fear conditioning test (effect of sex, F(1,40) = 21.58; P < 0.001). In contextual freezing (E), both males and females showed greater freezing to the 0.35 and 0.90 mA shock intensity compared to the no-shock group (*P < 0.05, ***P < 0.001, no shock group vs. 0.35 and 0.90 mA, respectively). (G) 3Gy irradiated females showed deficits in contextual fear conditioning (P < 0.05 vs. sham-irradiated females). (H) Cued fear conditioning was not impaired by irradiation. (For A–C and G–H, N = 6–8 mice/sex/dose).