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. 2022 Apr 26;14:59. doi: 10.1186/s13195-022-00999-5

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Age-related changes in the perivascular AQP4 polarization in the mouse cortex (A,B): Representative confocal micrographs of AQP4 IF labeling in 3-month-old (A) and 15-month-old (B) mouse cortex. Scale bars: 100 μm. C In capillary-associated astrocytes, the AQP4 IF at the perivascular (PV) endfeet was significantly reduced in aged animals (P = 0.0097, mixed effects model with Sidak post hoc test), while the AQP4 IF in the surrounding non-perivascular neuropil was unchanged. D Cross-sectional AQP4 IF projections (yellow lines in A,B) across large cortical vessels were quantified and averaged between 3-month (blue, 104 vessels from 6 animals) and 15-month (grey, 55 vessels from 6 animals) old mice. E Segmentation of projections into PV Endfeet (0–1.5 μm from the vessel wall), the PV Astrocyte (1.5–20 μm from the vessel wall), and the surrounding neuropil (20–68 μm from the vessel wall) showed that along large cortical vessels, PV Astrocyte AQP4 IF was significantly higher in the aged mice (P = 0.004, mixed effects model with Sidak post hoc correction). Plot at left shows values for all vessels measured, plot at right shows averaged values per animal. F Among large cortical vessels, PV Endfoot (left) or Neuropil (right) IF was not related to vessel diameter. PV Astrocyte IF was significantly associated with increasing vessel diameter (middle). This association was significantly (P = 0.0422) steeper for 15-month-old (gray; P = 0.0001, R² = 0.2410) compared to 3-month-old animals (blue; P = 0.0593, R² = 0.03444)