Fig 2: Water maze speed and distance were modestly affected by CCI but not by ApoE deficiency.a, c During acquisition, injured mice swam longer distances to reach the hidden platform as compared to the control groups, however, there was no significant CCI effect on swim distance in mice lacking astrocytic ApoE. The injury also resulted in slower swimming speed despite the presence of astrocytic ApoE. b, d In reversal learning trials, all mice swam similar distance to reach the new position of the platform. Interestingly, the swimming speed was slower in Ctr–CCI group. However, there was no difference observed between cKO-Sham and cKO–CCI. Data are presented as means ± SEM.

Fig 3: Tamoxifen and aldh1l1-creERT-dependent knockdown of ApoE expression in astrocytes.a Quantitative RT-PCR demonstrates a significant reduction in ApoE mRNA in the hippocampus in conditional knockout mice after treatment with tamoxifen. b Significant reduction in the number of ApoE-expressing cells in the hippocampus in aldh1l1-creERT; apoef/f mice in both sham-operated and CCI mice. c–e Seven weeks after tamoxifen in control littermates, ApoE expression was observed in most aldh1l1-dependent tdTomato-expressing cells in the hippocampus, as shown by arrows. f–h In apoef/f mice, ApoE expression in tdTomato-expressing cells is dramatically reduced. i–k In the absence of aldh1l1-creERT, the expression of ApoE in the hippocampus remained unchanged in mice receiving tamoxifen and the expression of cre-dependent tdTomato was not observed. This indicates that no spontaneous recombination of loxp-flanked DNA fragments was observed. Data are presented as means ± SEM, *P < 0.05; **P < 0.01; ***P < 0.001. Scale bar = 50 µm.

Fig 4: The morphology of Golgi–Cox-stained neurons in the hippocampus mice without astrocytic ApoE.a–h The left panels demonstrate Golgi–Cox-stained neurons in the dentate gyrus and the right panel depicts individual analyzed neurons. i The dendritic trees of the existing neurons in the dentate gyrus were impaired significantly in CCI groups but were not affected by the reduction of astrocytic ApoE. j, k CCI resulted in shorter total length and fewer nodes in the existing neurons in the dentate gyrus despite of the genotype. Data are presented as means ± SEM. ****P < 0.0001. Scale bar in (h) = 100 µm.

Fig 5: Impaired spatial learning in astrocytic ApoE-deficient mice was worsened by CCI in the Morris water maze test.a Astrocytic ApoE deficiency did not affect spatial memory in uninjured mice after acquisition training but did impair memory in cKO mice with CCI. b Astrocytic ApoE deficiency alone was sufficient to impair reversal memory. The same impairment was seen in cKO mice with or without CCI. c, e During the acquisition training session, injured mice exhibited longer latency to the platform than sham-operated mice. This was significant in controls and approaching significance in cKO mice. d, f During the reversal training session, no difference was observed. Data are presented as means ± SEM. *P < 0.05.