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. 2021 Nov 11;18(4):2484–2503. doi: 10.1007/s13311-021-01151-1

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© The Author(s) 2021

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/.

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Fig. 4 — Systemic administration of the AAV-hE2F4DN vector attenuates microgliosis and reactive astrocytosis in the cerebral cortex of h5xFAD mice. (a) Representative Iba1 immunostaining in the cerebral cortex of 6.5-month-old h5xFAD mice administered with either vehicle or AAV-hE2F4DN at 1.5 months. Notice the decreased area occupied by Iba1-positive labeling in the cerebral cortex of h5xFAD mice expressing neuronal hE2F4DN. Inserts show Iba1 staining of the indicated dashed boxes. Layers are indicated with Arabic numbers. (b) Percentages of the areas occupied by Iba1 immunostaining in the indicated cortical layers (F_(1,25) = 20.1462; p = 0.0001; unbalanced two-way ANOVA). Numbers refer to the different cortical layers. (c) Representative GFAP immunostaining in the cerebral cortex of 6.5-month-old h5xFAD mice administered with either vehicle or AAV-hE2F4DN at 1.5 months. Notice the decreased GFAP-positive labeling and reactivity of astrocytes in the cerebral cortex of h5xFAD mice expressing neuronal hE2F4DN. Inserts show GFAP staining of the indicated dashed boxes. Layers are indicated with Arabic numbers. (d) Percentages of the areas occupied by GFAP immunostaining in the indicated cortical layers (F_(1,25) = 13.9501; p = 0.001; unbalanced two-way ANOVA). Numbers refer to the different cortical layers. *p < 0.05, **p < 0.01; unbalanced two-way ANOVA followed by post hoc two-tailed Student’s t test. Scale bar, 50 μm. (e, f) Systemic administration of the AAV-hE2F4DN vector leads to a tendency for the attenuation of microgliosis and reactive astrocytosis in the hippocampus of h5xFAD mice. Percentage of area occupied by Iba1 immunostaining (e). Percentage of area occupied by GFAP immunostaining (f)