Figure 2.

Astrocyte-specific SOD2-KO impairs cognitive performance in males. A–Q, Behavioral data in the PhenoTyper (A–M) and RAWM (N–Q) are represented below. A, B, Circadian activity (distance moved) of aSOD2-KO (males: n = 11, blue square; females: n = 11, red square) and age-matched control (males: n = 7, blue circle; females: n = 9, red circle) males (A) and females (B) plotted per hour over a 90 h period in the PhenoTyper. Young (6 months) C57BL/6J (males: n = 12, blue dashed line; females: n = 12, red dashed line) mice served as reference controls for optimal activity and cognitive performance. C, D, Cumulative learning index during initial discrimination (acquisition; 0–49 h) and reversal (50–89 h) phases show a decline in aSOD2-KO males (C), but not in females (D), over the 90 h testing period. Black bars near the x-axis indicate dark periods of the light/dark cycle. E, Cognitive flexibility measured during hours 51–61 of the reversal phase is reduced in aSOD2-KO males (p = 0.040) but not in females. F, Percentage (%) of incorrect entries (left + middle entries/total entries) calculated during hours 51–61 of the reversal phase is increased in males (p = 0.040) but not in females. G, Bar plot depicting no changes in the initial learning rate of males and females assessed using the PhenoTyper between aSOD2-KO and age-matched controls. H, Bar plots depicting the distanced moved of males (p = 0.033) and females during the dark phase of the reversal phase in the PhenoTyper. I, Bar plots depicting differences between groups in the velocity of males and females during the dark phase of the PhenoTyper. J–M, Survival graphs depicting the number of entries to reach 80% criteria in the acquisition phase and reversal phase for males (E, F; n = 7–11/group) and females (G, H; n = 9–11/group). Young controls (6 months of age; n = 12/sex) were used as reference for optimal performance. N, Total errors (number of entries into incorrect arms) plotted during acquisition (learning) and reversal learning in the radial arm water maze in males (n = 8-9/group) and females (n = 6-7/group). Male aSOD2-KO mice showed a significant decline in reversal learning (p = 0.0058) compared with controls. O, Distance moved (path length) plotted during acquisition (learning) and reversal learning in the radial arm water maze in males and females. Male aSOD2-KO showed an increase in reversal learning path length compared with controls (p = 0.051). P, Bar plots depicting the nonmoving duration (NMD) in the radial arm water maze showed no differences between aSOD2-KO and control in males (H; n = 8–9/group) and females (I; n = 6–7/group). Q, Bar plots depicting the latency to target showed no differences in the initial and reversal phases in either groups for males and females in the radial arm water maze (n = 8–9/group). For graphs I–Q, colored bars represent the following: males (blue), females (red), aSOD2-KO (shaded). Error bars depict the mean ± SEM. Significance was tested using unpaired Student's t test (*p < 0.05; **p < 0.01).