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. 2021 Jun 28;15:668286. doi: 10.3389/fncel.2021.668286

FIGURE 2.

FIGURE 2

AM251 treatment reverses radiation-induced cognitive dysfunction. NOR: Total exploration time did not differ between all treatment groups (A1–D1). At 4 weeks postirradiation, the preference for novelty was reduced significantly in irradiated mice, an effect that was ameliorated by short-term AM251 treatment (A2), evidenced further by follow-up analysis of the DI (A3). However, this same short-term AM251 treatment was unable to maintain efficacy 12 weeks following irradiation (B2). While radiation-induced decrements persisted, the benefits of AM251 waned over this extended interval (B3). Nonetheless, long-term AM251 treatments were found to maintain neurocognitive benefits (C2), where radiation-induced decrements in the DI measured 13 weeks afterward were ameliorated significantly by AM251 (C3). Delayed AM251 treatment was not effective in resolving radiation-induced cognitive deficits 13 weeks postirradiation (D1–D3). OiP: Similarly, irradiation and/or AM251 treatment had no effect on total exploration time in the OiP task (E1–H1). At 6 weeks following irradiation, the preference for novelty was reduced significantly in irradiated mice, which was ameliorated by short-term AM251 treatment (E2), as indicated further by subsequent analysis of the DI (E3). When this same short-term AM251 treatment was assessed 12 weeks later, radiation-induced deficits persisted while AM251 failed to show efficacy (F2–F3). Long-term AM251 treatments were again found to restore neurocognitive benefits 13 weeks following irradiation (G2), where radiation-induced deficits in the DI found 13 weeks later were ameliorated significantly by AM251 (G3). Delayed AM251 treatment was not found to be effective in improving behavioral performance on the OiP task 13 weeks after irradiation (H1–H3). Data presented as means ± SEM, N = 8–12. P-values for total exploration time (A1–D1) and DI (E1–H1) were derived from two-way ANOVA followed by Bonferroni correction for multiple comparisons. While three-way ANOVA following Sidak post hoc analyses was carried out using time spent exploring novel/familiar object × irradiation (A2–D2;E2–H2). **P < 0.01; ***P < 0.001; and ****P < 0.0001.