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. 2022 Aug 2;12(8):e1003. doi: 10.1002/ctm2.1003

FIGURE 4.

FIGURE 4

Overexpressing nuclear factor‐erythroid 2–related factor 2 (NRF2) ameliorates P301S‐induced memory loss. (A) Experimental procedures of virus injection and behaviour tests. AAV‐P301S‐EGFP or AAV‐EGFP, and AAV‐NRF2‐mCherry or AAV‐mCherry were stereotaxically injected into the hippocampal CA3 region of 2‐month‐old C57BL/6J mice, and learning and memory were detected 4 weeks later. (B‐D) Efficiency of virus infection and P301S or NRF2 overexpression at CA3 were confirmed by fluorescence imaging or Western blotting at 4 weeks after virus infection. One‐way analysis of variance (ANOVA), F(3, 8) = 45.3, p < .01; n = 3. (E and F) Overexpressing NRF2 ameliorated P301S‐induced malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity in CA3 of C57BL/6J mice. One‐way ANOVA, [MDA] F(3, 8) = 23.13, p =.0016; [SOD] F(3, 8) = 19.78, p =.0038; n = 3. (G and H) Knockdown NRF2 decreased mice's staying time in centre zone of the box of open field test (OFT). One‐way ANOVA, F(3, 36) = 5.593, p = .0260; n = 10. (I and J) Overexpressing NRF2 increased mice's staying time in centre zone of the box of OFT. One‐way ANOVA, F(3, 36) = 3.488, p = .0255; n = 9–10 mice in each group. (K and L) Overexpressing NRF2 reversed P301S‐induced novel object recognition (NOR) impairments in C57BL/6J mice compared with the vehicle controls. Cartoons show paradigms of the NOR. One‐way ANOVA, F(3, 40) = 5.807, p = .0022; n = 10–11 mice in each group. (‐M and N) Overexpressing NRF2 ameliorated P301S‐induced spatial learning deficit in Morris water maze (MWM) test. Cartoons show paradigms of the MWM test. Two‐way ANOVA × days, F(3, 168) = 6.431, p = .0004; n = 9–10 mice in each group. (O–R) Overexpressing NRF2 ameliorated P301S‐induced spatial memory deficits in C57BL/6J mice shown by the increased platform crossing time (O), increased duration in the target quadrant (P) and decreased time to reach the platform location (latency) (Q) in water maze test detected at day 7 after removed the platform; the swimming speed was not changed (R). One‐way ANOVA, [platform crossing times] F(3, 36) = 5.795, p = .0024; [duration] F(3, 36) = 5.952, p = .0021; [latency] F(3, 36) = 5.018, p = .0024; n = 10 mice in each group. (S and T) Overexpressing NRF2 ameliorated P301S‐impaired fear conditioning test (FCT). One‐way ANOVA, F(3, 36) = 4.089, p = .0135; n = 10–11 mice in each group. * p < .05, ** p < .01 versus VEC + mCherry; # p < .05, ## p < .01 versus P301S + mCherry. Data were presented as mean ± SEM.