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Glial cells are key players in this process. However, the effects of peripheral infection on glial activation and brain function remain unknown. Here, we showed that varying degrees of peripheral infection had different effects on the regulation of brain functions by microglia-dependent and -independent mechanisms. Acute mild infection (one-day LPS challenge: 1LPS) exacerbated middle cerebral artery occlusion (MCAO) injury, and severe infection (four-day LPS challenge: 4LPS) for one week suppressed it. MCAO injury was assessed by triphenyltetrazolium chloride staining. We observed early activation of microglia in the 1LPS and 4LPS groups. Depleting microglia with a colony-stimulating factor-1 receptor (CSF1R) antagonist had no effect on 1LPS-induced brain injury exacerbation but abolished 4LPS-induced protection, indicating microglial independence and dependence, respectively. Microglia-independent exacerbation caused by 1LPS involved peripheral immune cells including macrophages. RNA sequencing analysis of 4LPS-treated microglia revealed increased factors related to anti-inflammatory and neuronal tissue repair, suggesting their association with the protective effect. In conclusion, varying degrees of peripheral inflammation had contradictory effects (exacerbation vs. protection) on MCAO, which may be attributed to microglial dependence. Our findings highlight the significant impact of peripheral infection on brain function, particularly in relation to glial cells.<\/jats:p>","DOI":"10.3390\/ijms242417597","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T03:59:24Z","timestamp":1702871964000},"page":"17597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Severity of Peripheral Infection Differentially Affects Brain Functions in Mice via Microglia-Dependent and -Independent Mechanisms"],"prefix":"10.3390","volume":"24","author":[{"given":"Yen-Phung","family":"Le","sequence":"first","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kozo","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijay","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Miyakawa","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6448-1304","authenticated-orcid":false,"given":"Youichi","family":"Shinozaki","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-6155","authenticated-orcid":false,"given":"Eiji","family":"Shigetomi","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-3106","authenticated-orcid":false,"given":"Schuichi","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan"},{"name":"GLIA Center, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e46171","DOI":"10.15252\/embr.201846171","article-title":"Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures","volume":"19","author":"Sousa","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12974-015-0332-6","article-title":"Systemic inflammation and microglial activation: Systematic review of animal experiments","volume":"12","author":"Hoogland","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/j.immuni.2021.09.014","article-title":"Microglia: Immune and non-immune functions","volume":"54","author":"Borst","year":"2021","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1471-4159.2012.07664.x","article-title":"Glial cells in (patho)physiology","volume":"121","author":"Parpura","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nature01786","article-title":"P2X(4) receptors induced in spinal microglia gate tactile allodynia after nerve injury","volume":"424","author":"Tsuda","year":"2003","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1038\/s41467-019-13812-z","article-title":"Dual microglia effects on blood brain barrier permeability induced by systemic inflammation","volume":"10","author":"Haruwaka","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12540","DOI":"10.1038\/ncomms12540","article-title":"Microglia contact induces synapse formation in developing somatosensory cortex","volume":"7","author":"Miyamoto","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The classical complement cascade mediates CNS synapse elimination","volume":"131","author":"Stevens","year":"2007","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/nature05704","article-title":"UDP acting at P2Y(6) receptors is a mediator of microglial phagocytosis","volume":"446","author":"Koizumi","year":"2007","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Saito, K., Shigetomi, E., Shinozaki, Y., Kobayashi, K., Parajuli, B., Kubota, Y., Sakai, K., Miyakawa, M., Horiuchi, H., and Nabekura, J. (2023). Microglia sense astrocyte dysfunction and prevent disease progression in an Alexander disease model. Brain, in press.","DOI":"10.1093\/brain\/awad358"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1523\/JNEUROSCI.6221-11.2012","article-title":"Genomic Analysis of Reactive Astrogliosis","volume":"32","author":"Zamanian","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","article-title":"Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability, Unmasking a Microglia Progenitor Cell in the Adult Brain","volume":"82","author":"Elmore","year":"2014","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","article-title":"Innate immune memory in the brain shapes neurological disease hallmarks","volume":"556","author":"Wendeln","year":"2018","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s11481-009-9164-4","article-title":"Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain","volume":"4","author":"Colton","year":"2009","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pharmthera.2003.08.003","article-title":"Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: Roles of the receptor complex","volume":"100","author":"Fujihara","year":"2003","journal-title":"Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"G22","DOI":"10.1152\/ajpgi.00229.2017","article-title":"Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM\/DSS mouse model of colon cancer","volume":"314","author":"Bader","year":"2018","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12974-016-0493-y","article-title":"Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A","volume":"13","author":"Liu","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1016\/j.celrep.2017.11.058","article-title":"Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts","volume":"21","author":"Boutej","year":"2017","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8714","DOI":"10.1073\/pnas.1218856110","article-title":"Activated microglia enhance neurogenesis via trypsinogen secretion","volume":"110","author":"Nikolakopoulou","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e66738","DOI":"10.7554\/eLife.66738","article-title":"Subventricular zone\/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave","volume":"10","author":"Hohsfield","year":"2021","journal-title":"elife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s12974-022-02532-9","article-title":"Repopulated microglia induce expression of Cxcl13 with differential changes in Tau phosphorylation but do not impact amyloid pathology","volume":"19","author":"Karaahmet","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1021\/acschemneuro.0c00567","article-title":"DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway","volume":"12","author":"Wang","year":"2021","journal-title":"Acs Chem. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715311","DOI":"10.3389\/fimmu.2021.715311","article-title":"p38 MAP Kinase Signaling in Microglia Plays a Sex-Specific Protective Role in CNS Autoimmunity and Regulates Microglial Transcriptional States","volume":"12","author":"McGill","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12974-020-01774-9","article-title":"Transcriptomic profiling of microglia and astrocytes throughout aging","volume":"17","author":"Pan","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.immuni.2020.09.018","article-title":"Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge","volume":"53","author":"Shemer","year":"2020","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11706","DOI":"10.1523\/JNEUROSCI.0730-12.2012","article-title":"Lipopolysaccharide-Induced Microglial Activation and Neuroprotection against Experimental Brain Injury Is Independent of Hematogenous TLR4","volume":"32","author":"Chen","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","article-title":"New tools for studying microglia in the mouse and human CNS","volume":"113","author":"Bennett","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23336","DOI":"10.1073\/pnas.1922788117","article-title":"CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages","volume":"117","author":"Lei","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0304-3940(94)90933-4","article-title":"Penetration of Interleukin-6 across the Murine Blood-Brain-Barrier","volume":"179","author":"Banks","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.nbd.2009.07.031","article-title":"The blood-brain barrier and immune function and dysfunction","volume":"37","author":"Banks","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e20220525","DOI":"10.1084\/jem.20220525","article-title":"Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes","volume":"220","author":"Culemann","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with Ischemia-A Delay of Lethal Cell Injury in Ischemic Myocardium","volume":"74","author":"Murry","year":"1986","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0006-8993(90)90189-I","article-title":"Ischemic Tolerance Phenomenon Found in the Brain","volume":"528","author":"Kitagawa","year":"1990","journal-title":"Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0006-8993(91)91596-S","article-title":"Ischemic Tolerance Phenomenon Detected in Various Brain-Regions","volume":"561","author":"Kitagawa","year":"1991","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1097\/01.WCB.0000040942.89393.88","article-title":"Ischemic tolerance","volume":"22","author":"Kirino","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1161\/01.STR.0000080381.76409.B2","article-title":"Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin","volume":"34","author":"Prass","year":"2003","journal-title":"Stroke"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1097\/00004647-200204000-00003","article-title":"Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain","volume":"22","author":"Bernaudin","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0306-4522(93)90138-6","article-title":"Temporal Profile of Heat-Shock Protein-70 Synthesis in Ischemic Tolerance Induced by Preconditioning Ischemia in Rat Hippocampus","volume":"56","author":"Liu","year":"1993","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1038\/jcbfm.2010.18","article-title":"Activation of NR2A receptors induces ischemic tolerance through CREB signaling","volume":"30","author":"Terasaki","year":"2010","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1161\/01.STR.0000063404.27912.5B","article-title":"Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats","volume":"34","author":"Horiguchi","year":"2003","journal-title":"Stroke"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/sj.jcbfm.9600262","article-title":"Resveratrol mimics ischemic preconditioning in the brain","volume":"26","author":"Raval","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.3949\/ccjm.75.Suppl_2.S77","article-title":"Preconditioning paradigms and pathways in the brain","volume":"75","author":"Shpargel","year":"2008","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1097\/00004647-199906000-00004","article-title":"Cerebrovascular hemodynamics and ischemic tolerance: Lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to changes in severity of the initial ischemic insult, but is associated with preservation of microvascular perfusion","volume":"19","author":"Dawson","year":"1999","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1161\/01.STR.0000143450.04438.ae","article-title":"Endotoxin preconditioning prevents cellular inflammatory response during ischemic neuroprotection in mice","volume":"35","author":"Rosenzweig","year":"2004","journal-title":"Stroke"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3171\/jns.2005.103.4.0715","article-title":"Differences in infarct evolution between lipopolysaccharide-induced tolerant and nontolerant conditions to focal cerebral ischemia","volume":"103","author":"Furuya","year":"2005","journal-title":"J. Neurosurg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0006-8993(96)01383-2","article-title":"Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats","volume":"748","author":"Tasaki","year":"1997","journal-title":"Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1523\/JNEUROSCI.4218-14.2015","article-title":"Astrocyte-Mediated Ischemic Tolerance","volume":"35","author":"Hirayama","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/glia.23109","article-title":"Hypoxia-Independent Mechanisms of HIF-1\u03b1 Expression in Astrocytes after Ischemic Preconditioning","volume":"65","author":"Hirayama","year":"2017","journal-title":"Glia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1002\/glia.23998","article-title":"Mechanisms underlying sensitization of P2X7 receptors in astrocytes for induction of ischemic tolerance","volume":"69","author":"Hirayama","year":"2021","journal-title":"Glia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"813536","DOI":"10.3389\/fimmu.2021.813536","article-title":"Multifocal Cerebral Microinfarcts Modulate Early Alzheimer\u2019s Disease Pathology in a Sex-Dependent Manner","volume":"12","author":"Lecordier","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.23529","article-title":"Macrophages prevent hemorrhagic infarct transformation in murine stroke models","volume":"71","author":"Gliem","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1002\/jnr.23448","article-title":"Lipopolysaccharide Preconditioning Facilitates M2 Activation of Resident Microglia After Spinal Cord Injury","volume":"92","author":"Hayakawa","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0304-3940(98)00537-0","article-title":"IL-10 reduces rat brain injury following focal stroke","volume":"251","author":"Spera","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.15252\/embj.201696056","article-title":"A novel microglial subset plays a key role in myelinogenesis in developing brain","volume":"36","author":"Wlodarczyk","year":"2017","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.abf6805","article-title":"A spinal microglia population involved in remitting and relapsing neuropathic pain","volume":"376","author":"Kohno","year":"2022","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.celrep.2014.09.032","article-title":"Nonclassical Ly6C\u2212 Monocytes Drive the Development of Inflammatory Arthritis in Mice","volume":"9","author":"Misharin","year":"2014","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1038\/nn.4160","article-title":"Cell type- and brain region-resolved mouse brain proteome","volume":"18","author":"Sharma","year":"2015","journal-title":"Nat. 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