Extended Data Fig. 10 | Reactive microglia in different neuroinf lammatory
and neurodegenerative conditions show a reduction in Entpd1 and P2ry12
expression that is associated with an A 1 R-dependent increase in D1 neuron
responses. a-g, Changes in Entpd1 and P2r y12 gene expression are shown in:
a, RNA extracted from whole striatum of 6-month old control mice and Q175
(Huntington’s disease) mice^94 (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 Disease^95 (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 model^39 (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 neurons^39 (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 expression^39 (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 5x fAD mice^96 (Entpd1:
P < 0.0001; P2ry12: P < 0.0001; n = 893 single microglia, fold change and P-value
provided in publication). g, FACS-sorted CD11b+CD45int single microglia in
control and LPS-injected mice (4 mg kg–1)^97 (Entpd1: P < 0.0001; P2r y12:
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 5x fAD Alzheimer’s mice (i) that is prevented by co-
administration of an A 1 R 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 inf lammatory
and/or neurodegenerative diseases (right). All statistical tests are two-tailed;
Data shown as mean ± s.e.m.