The metabolic regulator USF-1 is involved in the control of affective behaviour in mice

Figures

• 

  Fig. 1. USF-1 deficiency ameliorates depression-like and anxiety-like behaviours. A Percentage (%) of immobility in the Forced Swim Test. B Latency to feed (s) in theNovelty Suppressed Feeding (NSF) test. C Post-NSF home-cage food consumption (g). D Percentage (%) of openarm entries in the Elevated Plus Maze (EPM). E Representative tracking images from the EPM. F Percentage (%) of sucrose preference G Ambulatory distance travelled in the Open Field (m). H Latency to fall (s) in the Rota Rod. All data are presented as mean ± SEM, n = 6–17 mice/group. Data are analysed by two-way ANOVA (genotype × sex). Only significant main effects of genotype are displayed; **p < 0.01, ***p < 0.001.

• 

  Fig. 2. Surgical removal of interscapular BAT depots does not alter the behavioural phenotype of USF-1 KO mice. A Schematic illustration of the experimental procedure and timeline. WT and USF-1 KO mice were either subjected to surgical removal of interscapular BAT (iBATx) or to sham surgeries. The behavioural consequences of iBATx were evaluated 6 weeks after in the Forced Swim (FST) and Elevated Plus Maze (EPM) tests. B No sign of iBAT regeneration 6 weeks after surgical removal. C Percentage (%) of immobility in the FST. D Percentage (%) of open-arm entries in the EPM. Data are presented as mean ± SEM. Data were analysed by two-way ANOVA (genotype × iBATx). Only significant main effects of genotype are displayed. n = 5–9 female mice/group.; **p < 0.01, ***p < 0.001.

• 

  Fig. 3. Adult hippocampal neurogenesis is not affected by USF-1 deficiency. A Diagrammatic representation of the experimental protocol. For the proliferation paradigm, mice were injected 4 times with BrdU, with a 2 h interval and euthanized 24 h after the last injection. For the survival paradigm, mice were injected twice daily, for 3 days and euthanized 14 days after the first injection. B Number of BrdU-positive cells in the proliferation paradigm, normalized to the size of the counted area. n = 8–9 mice/genotype (WT males:4; WT females: 4; USF-1 KO males:4; USF-1 KO females: 5). C Number of BrdU-positive cells in the survival paradigm, normalised to the size of the counted area. n = 5–6 mice/genotype (WT males:3; WT females: 2; USF-1 KO males:3; USF-1 KO females: 3). D Number of double-labelled BrdU and NeuN cells in the survival paradigm, normalised to the size of the counted area. n = 5–6 mice/genotype (WT males:3; WT females: 2; USF-1 KO males:3; USF-1 KO females: 3). D’ Representative microscopy image of a WT hippocampus; Red: BrdU; Green: NeuN; Blue: Dapi; scalebar: 500 µm. E Number of double-labelled BrdU and GFAP cells in the survival paradigm, normalised to the size of the…

• 

  Fig. 4. The transcriptomic profile of the USF-1 KO hippocampus presents with altered expression of Xlr genes. A Heatmap and B graphical illustration representing differentially expressed genes (DEG) in hippocampal tissue of USF-1 KO mice. C Relative hippocampal expression of xlr3b and D xlr4b in USF-1 KO and WT mice. n = 6 mice/genotype (WT males:3; WT females: 3; USF-1 KO males:3; USF-1 KO females: 3). Data are presented as mean ± SEM. Statistical significances resulting from student’s t-test are displayed; *p < 0.05, **p < 0.01, ***p < 0.001, n.s. not significant.

• 

  Fig. 5. USF-1 deficiency leads to stubbed dendritic length and complexity. Examples of Golgi-Cox stained hippocampal brain sections of A WT and A’ USF-1 KO mice (60× magnification; scalebar: 50 µm). Neurolucida reconstruction of pyramidal neurons in the hippocampus of B WT and B’ USF-1 KO (scalebar: 100 µm). C Cumulative dendritic length (µm). D Length of non-apical dendrites (µm). E Length of apical dendrites (µm). F Number of nodes. G Spine density (nr. of spines/10 µm). Data are presented as mean ± SEM. n = 14–27 sections/ group. Statistical significances resulting from student’s t-test are displayed; **p < 0.01, ***p < 0.001.