ApoE Regulates the Development of Adult Newborn Hippocampal Neurons

ApoE deficiency leads to a decrease in overall proliferation, the number of type 1 NSPCs, and type 1 NSPC proliferation in the dentate gyrus, while leaving the ability of newborn cells to survive and differentiate into granular neurons unimpaired. A–C, Unbiased stereological quantification of the number of BrdU-positive cells (A), the number of BrdU-Prox1 double-positive cells (B), and the percentage of BrdU-positive cells that also express Prox1 (C). D–K, Representative confocal images of the SGZ in WT and ApoE-deficient mice illustrate nestin-expressing (green), Ki67-expressing (red), and GFAP-expressing (blue) cells, along with a merged image of all channels. White arrows indicate nestin-Ki67-GFAP triple-positive cells, representing actively proliferating type 1 NSPCs. L–N, Unbiased stereological quantification of the number of Ki67-positive cells (L), the number of nestin-GFAP double-positive cells (M), and the number of nestin-GFAP-Ki67 triple-positive cells (N). Results are expressed as the mean ± SEM. Unpaired Student’s t tests, *p < 0.05. Scale bar, K, 50 µm.

The complexity as well as the total dendritic length of ApoE-deficient adult-born granule cells are significantly reduced. A, B, Representative 3D-reconstructed adult-born granule cells (4 weeks after stereotactic injections), one circle every 10 µm. C, Distance between the soma and the first dendritic division (in µm). D, Nodes were defined as the number of divisions of dendritic branches. E, Cumulative length of dendritic arborization (in µm). F, Span of the dendritic arborization when projected on two dimensions. G, Sholl analysis: the number of dendritic intersections as a function of the distance from the soma: wild type, 78 neurons/4 mice; ApoE-deficient, 73 neurons/7 mice. Results are expressed as the mean ± SEM. Independent t test and two-way-ANOVA with uncorrected Fisher’s LSD post hoc tests were used: *p < 0.05, **p < 0.01, ***p < 0.001. Scale bar, B, 50 µm.

The complexity and the total dendritic length of ApoE4 adult-born granule cells are significantly reduced. A, B, Representative 3D-reconstructed adult-born granule cells (4 weeks after stereotactic injections), one circle every 10 µm. Representative picture of 4-week-old retrovirally labeled adult-born granule cells in the dentate gyrus. C, Distance between the soma and the first dendritic intersection (in µm). D, Nodes defined as the number of divisions of dendritic branches. E, Cumulative length of dendritic arborizations (in µm). F, Span of the dendritic arborizations when projected on two dimensions. G, Sholl analysis: number of dendritic intersections as a function of the distance from the soma. ApoE3, 75 neurons/6 mice; ApoE4, 69 neurons/4 mice. Results are expressed as the mean ± SEM. Independent t test and two-way ANOVA with uncorrected Fisher’s LSD post hoc tests were used: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Scale bar, B, 50 µm.