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. 2019 Oct 24;10:1269. doi: 10.3389/fphys.2019.01269

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Copyright © 2019 Denver, D’Adamo, Hu, Zuo, Zhu, Okuma, Kim, Castro, Jones, Leal, Mekkittikul, Ghadishah, Teter, Vinters, Cole and Frautschy.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Aquaporin-4 is elevated in the brains of FAD, with a further increase in SHRSP/FAD rats, while aquaporin-4 protein levels in plasma exosomes were elevated in SHRSP/FAD rats only. (A) Micrographs illustrate staining for Aqp-4, a membrane-bound protein in astrocyte end-feet. In WKY rats, staining was associated with evenly distributed small tubular vessels (black arrows), while in FAD rats, staining was in patches of fragmented vessels, tortuous thin astrocyte processes (red arrows) and swollen vessels (blue asterisks). In SHRSP rats, Aqp-4 staining was slightly increased and labeled distended but normally shaped tubular vessels (black arrows). There were more Aqp-4-positive amorphous patches in the hippocampus of FAD rats, an effect that was exacerbated in SHRSP/FAD rats (red arrows). Two-way ANOVA showed FAD (p < 0.0001) and SHRSP (p < 0.0001) effects for count and percent area. Post hoc analysis showed that in the hippocampus, Aqp-4 count (p < 0.001) and percentage area stained (p < 0.001) were significantly elevated in FAD, compared to WKY rats. This effect was further increased in SHRSP/FAD rats in which Aqp-4 count (p < 0.01) and percentage area stained (p < 0.01) were significantly increased, compared to FAD rats. In SHRSP/FAD rats, there were more structures stained positively for Aqp-4 (p < 0.001) and a higher percentage area stained (p < 0.001), compared to SHRSP. (B) Aqp-4 was also measured in hippocampal tissue lysates (mid right panel) and analyzed by two-way ANOVA (FAD × SHRSP × sex), which showed a significant main effect of FAD on the 150 kDa Aqp-4. Post hoc analysis demonstrated that Aqp-4 (150 kDa) was significantly elevated in the hippocampal tissue from FAD, compared to WKY and SHRSP rats (p < 0.01). (C) The 150 kDa Aqp-4 protein was also measured in brain-derived plasma exosomes (bottom panel) and two-way ANOVA (FAD × SHRSP × sex) demonstrated a significant interaction between FAD and SHRSP. Post hoc analysis showed that Aqp-4 (150 kDa) was significantly elevated in plasma exosomes from SHRSP/FAD rats, compared to FAD and SHRSP rats (p < 0.05). Data represent means ± SEM. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.