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. 2024 Jul 27;15:6340. doi: 10.1038/s41467-024-50466-y

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© The Author(s) 2024, corrected publication 2024

Open Access This 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. 8 — a Schematic illustration of activation of Gi signaling in A1AR deficit astrocytes experiment employing DREADD hM4Di and experimental plan. b Representative image of hM4Di expression indicated by mCherry in the Sox9⁺ astrocytes. Scale bar = 50 μm. c hM4Di was expressed in 94% of striatal astrocytes, with >84% specificity (n = 3 mice). d Representative images of immunolabeled reactive A1AR-deficient astrocytes by c-Fos immunostaining after LPS and CNO injection. Scale bar = 50 μm. e Activation of hM4Di increased c-Fos expression in hM4Di-mCherry⁺ A1AR-deficient astrocytes after LPS injection (n = 4 mice per group). f Representative images of immunoreactivity of p65 in Iba1⁺ microglia in Adora1 cKO mice with astrocytic tdT or hM4Di expression after LPS and CNO injection. Scale bars = 50 μm. Arrowheads indicates Iba1⁺ microglia with nuclear p65 expression. g Nuclear p65⁺ microglia was increased in hM4Di-expressing Adora1 cKO mice after LPS and CNO injection compared to ctl mice (n = 4 mice per group). h The expression of 40 cytokines in the striatum of AAV-infected ctl and Adora1 cKO mice was measured by a proteomic profiling assay after LPS and CNO injection. i Enhancing Gi signaling in Adora1 cKO mice increased cytokine expression after LPS and CNO injection (samples from 3 mice were pooled for each group). j Representative trajectory analysis digitally tracked movement of ctl and Adora1 cKO mice injected with LPS and CNO in the open-field test at 24 hpi. k, l Enhancing Gi signaling in A1AR-deficit astrocyte reduced locomotion in the open-field test (n = 12 mice in ctl-tdT+CNO group, n = 11 mice in Adora1 cKO-tdT+CNO group, n = 9 mice in ctl-hM4Di+CNO group, n = 13 mice in Adora1 cKO-hM4Di+CNO group). Summary data are presented as the mean ± SEM. Statistical significance in e, g was assessed using two tailed unpaired Student’s t test; statistical significance in k, l was assessed using a two-way ANOVA, Fisher’s LSD test, ns: p > 0.05. Source data are provided as a Source Data file. Panel a was created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.