Fig. 5: Overexpression of CREB in the CA1 region induces depression-like behaviors and increases PER2 levels.

A Timeline of the LV microinjections and the behavioral experiments. B Injection site of LV-CMV-CREB-EGFP (left panel, scale bar: 1 mm) and viral EGFP expression (right panel, scale bar: 100 µm) in the CA1 region of the rat brain. Representative western blots (C) and quantification of the relative protein levels of CREB in the CA1 at ZT02 (D) (n = 5 rats per group). The effects of CREB overexpression in the CA1 region (n = 9 rats per group) on sucrose preference (E), immobility time in FST (F), the number of entries (G) and time spent (H) in the open arms of EPM, total distance (I) and time spent in the central zone (J) of OFT. Representative western blots (K) and quantification of the relative protein levels of PER2 in the CA1 region at ZT02 (L) (n = 5–6 rats per group). D, F–L: Two-tailed Student’s t test, E: Mann–Whitney test: *P < 0.05, **P < 0.01). M Co-immunoprecipitation experiment conducted with lysates from rat hippocampal CA1 region showing that CREB1 and PER2 co-immunoprecipitate. N Co-immunoprecipitation experiment showing that PER1 and PER2 can also be co-immunoprecipitated with CREB1. Data are presented as mean ± SEM and the individual data points are depicted. See also Supplementary Fig. S5 and Supplementary Table S1. Some of the sketches were made with biorender.com.