Extended Data Fig. 10: Reactive microglia in different neuroinflammatory and neurodegenerative conditions show a reduction in Entpd1 and P2ry12 expression that is associated with an A₁R-dependent increase in D1 neuron responses.

a-g, Changes in Entpd1 and P2ry12 gene expression are shown in: a, RNA extracted from whole striatum of 6-month old control mice and Q175 (Huntington’s disease) mice⁹⁴ (Entpd1: P = 0.0001; P2ry12: P = 0.004; n = 8 mice, fold change and P-value provided in publication). b, RNA from FACS-sorted CD11b+/F4/80+ cortical and hippocampal microglia from 8.5-month old control and 5xfAD mouse model of Alzheimer’s Disease⁹⁵ (Entpd1: P = 0.009; P2ry12: P = 0.0035; n = 5 mice, fold change and P-value provided in publication). c, RNA from FACS-sorted forebrain microglia from 10-month old control and APP/PS1 Alzheimer’s disease mouse model³⁹ (n = 3 mice, Entpd1: P = 0.038; P2ry12: P = 0.023, unpaired two-tailed t-test). d, RNA from FACS-sorted FCRLS+ phagocytic and non-phagocytic microglia isolated after stereotaxic injection of apoptotic neurons³⁹ (n = 4 mice, Entpd1: P < 0.0001; P2ry12: P < 0.0001, unpaired two-tailed t-test). e, FACS-sorted FCRLS⁺ microglia in 24-month old control mice or APP/PS1 Alzheimer’s disease mouse model. Plaque associated microglia were identified and sorted based on CLEC7A expression³⁹ (n = 6 mice, Entpd1: P = 0.01; P2ry12: P < 0.0001, One-way ANOVA with Tukey’s post hoc test). f, Massively parallel single-cell RNA-seq (MARS-seq) from isolated homeostatic microglia and disease associated microglia (DAM) in 5xfAD mice⁹⁶ (Entpd1: P < 0.0001; P2ry12: P < 0.0001; n = 893 single microglia, fold change and P-value provided in publication). g, FACS-sorted CD11b⁺CD45^int single microglia in control and LPS-injected mice (4 mg kg^–1)⁹⁷ (Entpd1: P < 0.0001; P2ry12: P < 0.0001; n = 477 microglia from saline injected mice and 770 microglia from LPS injected mice, fold change and P-value provided in publication). h, i, Bar graphs show increased seizure susceptibility to D1 agonist administration (SKF81297, 5 mg kg^–1, i.p.) in LPS-injected (indicated doses, i.p.) (h) and 6-8-month old 5xfAD Alzheimer’s mice (i) that is prevented by co-administration of an A₁R agonist (CPA, 0.1 mg kg^–1, i.p.) (h, n = 10-22 male mice, P = 0.032, Chi-squared test; i, n = 5-10 mice per genotype, left, P = 0.031, Fisher’s exact test with Yates correction; right, P = 0.49, Fisher’s exact test with Yates correction). j, Scheme illustrating the model of microglia-mediated adenosine-controlled regulation of D1 neuron responses in the healthy striatum (left) and its potential dysfunction upon microglia activation during inflammatory and/or neurodegenerative diseases (right). All statistical tests are two-tailed; Data shown as mean ± s.e.m.

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