REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit anti-Iba1	WAKO	Cat# 019-19741, RRID:AB_839504
Rat anti-Lamp1	Santa Cruz Biotechnology	Cat# sc-19992, RRID:AB_2134495
Rat anti-MHCII	Santa Cruz Biotechnology	Cat# sc-59322, RRID:AB_831551
Rabbit anti-P2Y12	Thermo Fisher Scientific	Cat# PA5-77671, RRID:AB_2736305
Rat anti-CD68	Abcam	Cat# ab53444, RRID:AB_869007
Rabbit anti-Iba1	WAKO	Cat# 016-20001, RRID:AB_839506
Mouse anti-Drebrin	Enzo Lifesciences	Cat# ADI-NBA-110-E, RRID:AB_2039073
Chicken anti-GAPDH	Merck Millipore	Cat# AB2302, RRID:AB_10615768
Rabbit anti-Actin	Sigma-Aldrich	Cat# A2066, RRID:AB_476693
Mouse monoclonal IgG anti-Iba1	Millipore	Cat# MABN92, RRID:AB_10917271
Rabbit anti-NG2 Chondroitin Sulfate Proteoglycan	Millipore	Cat# ab5320, RRID:AB_91789
Rabbit anti-Cox2	Abcam	Cat# ab62331, RRID:AB_942121
Rabbit anti-PGE	Abcam	Cat# ab2318, RRID:AB_302974)
Guinea pig anti-Vglut1	Synaptic Systems	Cat# 135 304, RRID:AB_887878
Mouse anti-Psd-95	Thermo Fisher Scientific	Cat# MA1-045, RRID:AB_325399
Biological Samples
Human Samples used for Western Blotting and RNA sequencing	Table S3	N/A
Human Samples used for Immunohistochemistry	Table S3	N/A
Chemicals, Peptides, and Recombinant Proteins
PLX3397 (Pexidartinib)	Selleckem	Cat#S7818
Dimethyl Sulfoxide (DMSO)	Sigma-Aldrich	Cat#276855
Acetaminophen (APAP)	Sigma-Aldrich	Cat#A7085
Ruxolitinib	Sigma-Aldrich	Cat# S1378
Hoechst	Sigma-Aldrich	Cat#H6024
Paraformaldehyde	Sigma-Aldrich	Cat#158127
VECTASHIELD Mounting Medium	Vector Laboratories	Cat# H-1000, RRID:AB_2336789
Potassium dichromate	Sigma-Aldrich	Cat#207802
Mercuric chloride	Sigma-Aldrich	Cat#215465
Potassium chromate	Sigma-Aldrich	Cat#216615
Ammonium hydroxide	Sigma-Aldrich	Cat#221228
DPX-Mounting medium	Sigma-Aldrich	Cat#06522
NaCl	Sigma-Aldrich	Cat#71376
HEPES	Sigma-Aldrich	Cat# H3375
NP40	Sigma-Aldrich	Cat#74385
Sodiumdeoxycholate	Sigma-Aldrich	Cat#D6750
Pierce BCA assay	Thermo-Fisher	Cat#23225
NuPAGE LDS Sample Buffer	Thermo-Fisher	Cat#NP0007
1,4-Dithiothreitol	Sigma-Aldrich	Cat#DTT-RO Roche
NuPAGE 4-12% Bis-Tris Midi Protein gels	Thermo-Fisher	Cat#WG1402BOX
Nitrocellulose membrane	Sigma-Aldrich	Cat#GE10600001
Trizma	Sigma-Aldrich	Cat#T6066
Tween 20	Sigma-Aldrich	Cat# P7949
Nonfat dry milk	Euroclone	Cat#EMR180500
Sucrose	Sigma-Aldrich	Cat#S7903
Magnesium chloride hexadrydate	Sigma-Aldrich	Cat#M9272
Potassium chloride	Sigma-Aldrich	Cat#P9333
Sodium phosphate monobasic dihydrate	Sigma-Aldrich	Cat#71505
Calcium chloride dihydrate	Sigma-Aldrich	Cat#C3306
Sodium bicarbonate	Sigma-Aldrich	Cat#S5761
D(+) Glucose	Sigma-Aldrich	Cat#G7021
Ethylene glycol-bis(2-aminoethylether)-N,N,N,N-tetraacetic acid	Sigma-Aldrich	Cat#E4378
Adenosine 5′-triphosphate magnesium salt	Sigma-Aldrich	Cat#A9178
Potassium D-gluconate	Sigma-Aldrich	Cat#G4500
Guanosine 5′-triphosphate sodium salt hydrate	Sigma-Aldrich	Cat#G8877
Phosphocreatine disodium salt hydrate	Sigma-Aldrich	Cat#P7936
Capsazepine	Hello Bio	Cat#E0282-2-3
N-Oleoyldopamine (OLDA)	Tocris	Cat# 1641
AM-251	Sigma-Aldrich	Cat# A6226
AM630	Sigma-Aldrich	Cat# SML0327
Bicuculline methiodide	Hello Bio	Cat# HB0893
Tetradotoxin	Hello Bio	Cat# HB1035
Glutaraldehyde	Sigma-Aldrich	Cat#G5882
Bovine Serum Albumin	Sigma-Aldrich	Cat#A2153
Sodium Azide	Sigma-Aldrich	Cat#SX0299
Saponin	Sigma-Aldrich	Cat#47036
3,3′-Diaminobenzidine	Sigma-Aldrich	Cat#D8001
Hydrogen peroxide-18O2 solution	Sigma-Aldrich	Cat#609978
Osmium tetroxide	Sigma-Aldrich	Cat#O5500
Uranyl Acetate	Polysciences	Cat#21447-25
EPON resin	Sigma-Aldrich	Cat#45359
Percoll	Sigma-Aldrich	Cat#GE17-0891-01
Sodium deoxycholate	Sigma-Aldrich	Cat#D6750
Chloroacetamide	Sigma-Aldrich	Cat#C0267
Tris(2-carboxyethyl)phosphine hydrochloride	Sigma-Aldrich	Cat#C4706
Dako fluorescent medium	Dako North America	Cat#S3023
Critical Commercial Assays
SuperSignal West Pico PLUS Chemiluminescent Substrate detection system	Thermo-Fisher Scientific	Cat#34578
HRP/DAB (ABC) Detection IHC Kit	Abcam	Cat#AB64259
QuantSeq 3′ mRNA-Seq Library Prep Kit FWD	Lexogen	Cat#015
QuantiTect Reverse Transcription Kit	QIAGEN	Cat#205310
RayBio Mouse Inflammation Array 1 antibody	RayBiotech	Cat# AAM-INF-1-8, RRID:AB_10181099
Pierce BCA assay	Thermo-Fisher Scientific	Cat# 23225
FASP Protein Digestion Kit	Expedeon Inc	Cat# 44250
Deposited Data
Proteomics Dataset for microglia	This paper	PRIDE: PXD015113;
Proteomics Dataset for hippocampal tissues	This paper	PRIDE: PXD015148
RNaseq datasets	This paper	GEO Series accession number: GEO: GSE137939
Uncropped blot, qPCR information and results of cognitive performance regarding total distance traveled, total object exploration time and preference during acquisition trials	This paper	https://data.mendeley.com/datasets/gkbrjc8rmd/draft?a=4c602482-bb3a-442a-8a90-c43e8efa9f00
Experimental Models: Organisms/Strains
Mouse: B6.129S7-Dp(16Lipi-Zbtb21)1Yey/JB6.129S7-Dp(16Lipi-Zbtb21)1Yey/J	The Jackson Laboratory	Cat # JAX:013530; RRID:IMSR_JAX:013530
Mouse: C57BL/6J	The Jackson Laboratory	Cat# JAX:000664, RRID:IMSR_JAX:000664
Mouse: B6.129P2(Cg)-Cx3cr1tm1Litt/J	The Jackson Laboratory	Cat# JAX:005582, RRID:IMSR_JAX:005582
Mouse:B6EiC3Sn a/A-Ts(1716)65Dn/J	The Jackson Laboratory	Cat# JAX:001924, RRID:IMSR_JAX:001924
Mouse: (C57BL/6JEiJ x C3H/HeSnJ)F1/J	The Jackson Laboratory	Cat# JAX:001875, RRID:IMSR_JAX:001875
Oligonucleotides
primer: GAPDH forward: ATGAAGGGGTCA TTGATGG	Sigma-Aldrich	N/A
primer: GAPDH reverse: AGGTGAAGGTCG GAGTCAA	Sigma-Aldrich	N/A
primer: PPIA forward: TTCTGCTGTCTTTG GGACCT	Sigma-Aldrich	N/A
primer: PPIA reverse: CACCGTGTTCTTCG ACATTG	Sigma-Aldrich	N/A
primer:STAT3 forward: TGGTGTCTCCAC TGGTCTATC	Sigma-Aldrich	N/A
primer: STATE reverse: TCCGAATGCCTC CTCCTTGG	Sigma-Aldrich	N/A
primer:FCGR1A forward: GCGATACCATA GAGTCCAGATC	Sigma-Aldrich	N/A
primer: FCGR1A reverse: CCAAGTATGA GAGCAGCGTATC	Sigma-Aldrich	N/A
primer:IL4R forward: AGCCGAGCCTAGA AACTAACAC	Sigma-Aldrich	N/A
primer: IL4R reverse: TGACCACCCTCC CTGAAGT	Sigma-Aldrich	N/A
primer: MARCKSL1 forward:AACTGTGC TGTCCTTGTG	Sigma-Aldrich	N/A
primer: MARCKSL1 reverse: GAACCAG ATGGCTGATG	Sigma-Aldrich	N/A
primer: PECAM1 forward: AGCGTCATT GGCGTGTTG	Sigma-Aldrich	N/A
primer: PECAM1 reverse:GAGACATCT CCTTCCCGTTTACCT	Sigma-Aldrich	N/A
Software and Algorithms
Fiji ImageJ	Schindelin et al., 2012	https://fiji.sc/; RRID: SCR_002285
GraphPad PRISM	GraphPad Software Inc.	https://www.graphpad.com/scientific-software/prism/
Anymaze	Anymaze	http://www.anymaze.co.uk/index.htm
MaxQuant software	Cox and Mann, 2008	https://www.maxquant.org/
Uniprot mouse database	Uniprot Consortium	https://www.uniprot.org/
Perseus software	Tyanova et al., 2016	https://maxquant.net/perseus/
FastQC v0.11.3	Babraham Bioinformatics group	http://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Trim Galore software	Babraham Bioinformatics group	https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/
STAR v2.7	UCSC Genome Browser for human (hg38) genome build	https://genome.ucsc.edu/
EdgeR v3.26.8	Bioconductor	https://bioconductor.org/packages/release/bioc/html/edgeR.html
EWCE R package	Bioconductor	https://bioconductor.riken.jp/packages/3.4/bioc/html/EWCE.html
ClusterProfiler v3.0.4	Yu et al., 2012	https://www.rdocumentation.org/packages/clusterProfiler/versions/3.0.4
Beacon Designer software	Premier Biosoft	http://www.premierbiosoft.com/molecular_beacons/
qBasePlus software	Biogazelle	https://services.biogazelle.com/
Picky software	Zauber et al., 2018	N/A
Skyline software	MacCoss Lab Software	https://skyline.ms/project/home/begin.view?
Xcalibur Software	Thermo Fisher Scientific	OPTON-30965
Neurolucida	Mbf Bioscience	https://www.mbfbioscience.com/neurolucida
Other
TCS SP5 microscope	Leica Microsystems	https://www.leica-microsystems.com