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. 2021 May 27;23(9):1523–1536. doi: 10.1093/neuonc/noab131

Fig. 5.

Fig. 5

Fig. 5

Sex modulates the effects of metformin in the irradiated brain. We tested for the impact of biological sex on the MET16 and MET19 interactions with radiation treatment by evaluating the 3-way interaction term of sex, radiation condition, and metformin treatment (denoted as SEX:7Gy:MET16 and SEX:7Gy:MET19). In (A, B), the color map shows all structures that had a significant difference in the radiation-metformin interaction between males and females (FDR of 10%). Slice positions in (A) match those in Figure 2. Many regions were relatively larger in the early (P23) irradiated metformin-treated female brain compared to the irradiated metformin-treated male brain. However, a greater growth rate was observed in metformin-treated irradiated males compared to metformin-treated irradiated females, particularly for MET16. In (C, E), representative plots averaged over males and females show the time course of structure volumes for the primary somatosensory cortex (forelimb region) and stratum granulosum of the hippocampus in unirradiated vehicle-treated mice (0 Gy-VEH), irradiated vehicle-treated mice (7 Gy-VEH), unirradiated MET16- or MET19-treated mice (0 Gy-MET16 or 0 Gy-MET19) and irradiated MET16- or MET19-treated mice (7 Gy-MET16 or 7 Gy-MET19). The plots are repeated in (D, F), with panels separated by sex to show sex-dependent differences. Points and error bars represent the mean volume and bootstrapped 95% confidence intervals. Abbreviations: 0 Gy, unirradiated; 7 Gy, irradiated with a 7-Gy dose; MET16, treated with metformin starting at P16; MET19, treated with metformin starting at P19; S1, primary somatosensory cortex (forelimb region); SG, stratum granulosum of hippocampus.