Fig. 1: Sustained hippocampal microglial reactivity and reduced CA1 dendritic spines in Anti-Caspr2 mice. | Molecular Psychiatry

Fig. 1: Sustained hippocampal microglial reactivity and reduced CA1 dendritic spines in Anti-Caspr2 mice.

From: Captopril restores microglial homeostasis and reverses ASD-like phenotype in a model of ASD induced by exposure in utero to anti-caspr2 IgG

Fig. 1

A Representative confocal images of microglia from stratum radiatum of the CA1 hippocampal sections of P21 Control and Anti-Caspr2 male mice, as well as their respective Imaris surface renderings. Green-Iba1, Red- CD68. Scale bar 10 µm. B Sholl analysis of P21 microglia from Control (7–10 microglia from each mouse, total microglia = 49) and Anti-Caspr2 (6–9 microglia from each mouse microglia = 48). Mixed model analysis, ICC = 0, P = 0.007. C Quantification of CD68 occupancy (CD68 volume to the total volume of Iba1) in the CA1 from Control (8–10 microglia from each mouse, total microglia = 53) Ant-Caspr2 (6–10 microglia from each mouse, total microglia=48). Mixed model analysis, ICC = 0.948, P = 0.109. D Representative examples of Hippocampal CA1 pyramidal dendritic spines derived from Z-stacks in a tiled montage in Control and Anti-Caspr2. E Quantification of pyramidal neuronal dendritic spines density from the CA1 hippocampus of P21 Control (10–12 dendrites from each mouse, total dendrites=68) and Anti-Caspr2 (10–12 dendrites from each mouse, total dendrites=69) male mice. Mixed model analysis, ICC = 0.247 P < 0.0001. A-E Control, n = 6, Anti-Caspr2, n = 6. Each mouse represents a unique litter. F Representative of pyramidal neuronal tracings (Neurolucida 360) from the CA1 hippocampus of P21 Control and Anti-Caspr2 male mice. G Sholl analysis quantifies the total dendritic length (means ± SEM) in concentric rings (radius) from the cell body of pyramidal cells in the CA1 at P21 from Control (6–10 pyramidal neurons from each mouse, total = 35, n = 5 mice representing 5 litters) and Anti-Caspr2 (6–10 pyramidal neurons from each mouse, total=40, n = 6 mice, representing 6 litters). Mixed model analysis, ICC = 0.102, P = 0.876. H Representative confocal images of microglia from stratum radiatum of the CA1 hippocampal sections of adult (16 weeks) Control and Anti-Caspr2 male mice. Green - Iba1, Red - CD68. I, J Quantification of adult microglia morphology (I) and CD68 (J) scores in Control (Control, 12–14 microglia from each mouse, total microglia=66, n = 5 mice representing 3 litters) and Anti-Caspr2 (14 microglia from each mouse, total microglia=70, n = 5 mice representing 3 litters). I Mann-Whitney test, U = 3, P < 0.0001. J Mann-Whitney test, U = 932.5, P < 0.0001. K Brain coronal sections of statistically significant clusters (t-value =  1.6, P  <  0.05), with increased uptake of [11 C]PBR28 in Anti-Caspr2 adult males compared to Control overlaid onto Paxino atlas images for visualization. [11 C]PBR28 values were measured post hoc in these clusters (right) and in the contralateral “mirror” regions (left) and averaged for the individual mice. L Post hoc analysis of the averaged [11 C]PBR28 relative uptake in both hemispheres between Control (n = 9, representing 7 litters) and Anti-Caspr2 (n = 9,representing 8 litters). Unpaired t-test, t(16) = 3.149 P = 0.0062).

Back to article page