High dose zinc supplementation induces hippocampus-dependent memory impairment.

(A) T-maze task for working memory assessment of zinc supplemented mice (n = 8). Compared with control mice, high-dose zinc supplemented mice exhibited working memory deficit. (B–C) Contextual discrimination test of the mice (n = 16).High-dose zinc supplemented mice showed significantly lower discrimination ratio than the other two groups across the seven days of acquisition. Low-dose zinc supplemented mice showed better discrimination than control in the last three testing days (B). Seven days later, the discrimination was recorded again, control and low-dose zinc supplemented mice could discriminate the two contexts whereas high-dose zinc supplemented mice still could not (C). (D) Contextual fear conditioning test of the mice (n = 16). There was no difference in freezing ratio among the three groups. (E–F) Open field test of the mice (n = 16). There was no difference in locomotor habituation among the three groups (E); Low-dose zinc supplemented mice showed shorter time in the center square than control, indicating increased anxiety in this group. *, p<0.05; **, p<0.01;***, p<0.001 vs. control group.