Figure 1

Genetic deletion of Per2 in glia leads to depression resistant behavior. (A) Immunohistochemistry of sections from suprachiasmatic nuclei (SCN) of control (left panel) and GPer2 mice (middle and right panels) collected at ZT12. Sections were incubated with antibodies against PER2 (green) and glial fibrillary acidic protein (GFAP), a glial marker (red, left and right panels), or NeuN (red, middle panel), a neuronal marker. White arrows in the control panel (left) indicate overlapping PER2 and GFAP signal (yellow) in glial cells, green indicates neuronal PER2 signal and red astrocytic GFAP. In GPer2 sections, PER2 is mostly detected in neurons that are NeuN-positive, giving rise to the yellow color. In contrast, PER2 (green) is not seen in glial cells (red) of GPer2 mice, indicating a glial specific deletion of PER2. Scale bar: 100 µm. (B) Immunohistochemistry of sections from the dorsal striatum (DS) of control (left panel) and GPer2 mice (middle and right panels) collected at ZT12. Sections were stained with DAPI (blue) to reveal cell nuclei and were incubated with antibodies against PER2 (green) and GFAP (red, left and right panels) or NeuN (magenta, middle panel). The yellow color indicates overlapping signal of PER2 and GFAP in control animals (left panel) or PER2 and NeuN in neurons (middle panel). No yellow color in GPer2 sections stained for PER2 and GFAP is observed. Scale bar: 10 µm. (C) Immobility time in the forced swim test (FST) of GPer2 (GCre⁺ Per2^fl/fl, red) and control (GCre^- Per2^fl/fl, blue) animals are shown (n = 13 or 11, respectively, two-tailed t-test, **P < 0.01). (D) FST of the Cre-driver line (GCre⁺ Per2 WT) and the Per2 control line (GCre^- Per2 WT) are shown (n = 6, two-tailed t-test, no significant difference is observed). (E) FST of Per2 mutant (Per2^Brdm1, purple) mice and their littermate controls (WT, green) show a significant difference as previously observed²³ (n = 13 and 8, respectively, two-tailed t-test, ***P < 0.001). (F) Representative swimograms of GPer2 (GCre⁺ Per2 ^fl/fl, red) and control (GCre^- Per2 ^fl/fl, blue) animals. Note the longer stretches of immobility in the control animals (right panel, blue). (G) Representative swimograms of Per2 mutant (Per2^Brdm1, purple) mice and their littermate controls (WT, green). Note the longer stretches of immobility in the control animals (right panel, green).