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. 2017 Mar 29;140(5):1447–1465. doi: 10.1093/brain/awx060

Figure 8.

Figure 8

Pan-neuronal progranulin deficiency with Nestin-Cre impairs social dominance, nesting, and the amygdala response to a novel, social environment, and produces cortical astrogliosis.Nestin-Cre N-KO mice developed a losing phenotype in the tube test for social dominance (A, P = 0.0007), and a trend for reduced nesting behaviour (B, P = 0.057). Nestin-Cre N-KO mice also exhibited impaired activation of the amygdala after exposure to a novel, social environment (C, repeated measures ANOVA effect of genotype, P = 0.0092), with specific impairments in the central (P = 0.0167) and medial (P = 0.0225) amygdala. Representative images of c-Fos immunostaining are shown with lines drawn to illustrate boundaries between amygdala nuclei (D). The boxed areas in the central amygdala are enlarged in the panels below the top images. The scale bars in the larger image in D = 100 µm, and the scale bar in the smaller central amygdala image = 50 µm. For assessment of pathology, brains from 18–19 month-old Nestin-Cre N-KO mice and Cre– littermates were immunostained for markers of microgliosis (E, CD68) and astrogliosis (F, GFAP). The presence of autofluorescent lipofuscin granules was measured by imaging brain sections with an epifluorescence microscope (G). No differences were detected between in CD68 immunoreactivity (E) or lipofuscin accumulation (G) showing that neuronal progranulin deficiency is not sufficient to reproduce most of the pathology of Grn–/– mice. However, Nestin-Cre N-KO mice exhibited cortical astrogliosis (F, repeated measures ANOVA genotype × brain region interaction P = 0.0012). A limited number of brains from Grn–/– mice were processed in parallel with the sections to serve as a positive control, but were not included in the statistical analysis given the small sample size. Representative×20 images of CD68, GFAP, and lipofuscin are shown for each group. Scale bars = 50 µm. Tube test and nesting data were analysed by Mann-Whitney test, and c-Fos and pathology data were analysed by repeated measures ANOVA with Sidak’s post hoc test. n = 23–24 mice per genotype for the tube test, 24 per genotype for nesting, 16 per genotype for c-Fos, and 9–14 per genotype for pathology. BLA = basolateral amygdala; CeA = central amygdala; MeA = medial amygdala; Ctx = cortex; HPC = hippocampus; Thal = thalamus. *P < 0.05, **P < 0.01.