ライフサイエンスコーパス: microglial

1 nipulation afforded by such techniques allow microglial ablation before, during, and/or following ins

2 of pair-feeding, bone marrow-transplant, and microglial ablation implicate central and peripheral con

3 C neurons, alterations in hippocampal and LC microglial abundance, upregulated GFAP expression, degen

4 As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated me

5 dies reported conflicting findings regarding microglial activation and an in-depth profiling of those

6 rain administration of rIFN-beta resulted in microglial activation and complement C3-dependent synaps

7 -penetrant tetracycline antibiotic, inhibits microglial activation and enhances long-term potentiatio

8 tion recapitulated the effects of obesity on microglial activation and IL-1beta gene expression, and

9 ived cytokines correlated with the extent of microglial activation and mobilization, even in the abse

10 neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces ma

11 ipose NLRP3 impairs memory via IL-1-mediated microglial activation and suggest that NLRP3/IL-1beta si

12 ed Th1 infiltration but did not fully rescue microglial activation and white matter injury after TBI.

13 endocytic system, cholesterol metabolism and microglial activation as Abeta-independent regulators of

14 Brains show an early increase in microglial activation at the 0-day time point that persi

15 However, it is not known if microglial activation contributes to the transition from

16 monstrated progressive lysosomal storage and microglial activation despite a lack of cerebrocortical

17 ls measured during the diagnostic LP reflect microglial activation early on in MS and can be consider

18 ation of smoke and morphine exposure induces microglial activation following infection, as well as in

19 ce satellite cell and neuronal apoptosis and microglial activation in infected ganglia.

20 y cellular targets contributing to sustained microglial activation in neurodegenerative diseases, inc

21 mice, CD38 knockout (KO) mice showed reduced microglial activation in the facial nucleus, whereas the

22 nd reversed the enhanced neuronal damage and microglial activation in the GFAP-ARO-KO mice after GCI,

23 ng evidence for spatiotemporal regulation of microglial activation in this context.

24 Concomitant asymmetry of microglial activation indicates a neuroinflammatory comp

25 uated depressive-like behavior and inhibited microglial activation induced by CUS or LPS treatment.

26 tor release and decreased the astroglial and microglial activation induced by DSS.

27 Microglial activation is associated with SVD, particular

28 Expression levels of microglial activation markers, such as HLA-DRA, IL6, and

29 Chronic neuroinflammation with sustained microglial activation occurs following severe traumatic

30 Microglial activation occurs later than that of CECs, su

31 Microglial activation plays a central role in poststroke

32 these receptors might vary between different microglial activation states.

33 Microglial activation was particularly prominent in cere

34 ion, oligodendrocyte numbers, and effects on microglial activation were less dramatic.

35 gressive lysosomal storage, astrocytosis and microglial activation were observed.

36 Given the known association of microglial activation with advancing Parkinson's disease

37 g Th17 lymphocytes have reduced BBB leakage, microglial activation, and antibody infiltration into th

38 to blood-brain barrier permeability, injury, microglial activation, and CX3CR1-CCR2 signaling, focusi

39 l for selective CNS entry of autoantibodies, microglial activation, and neural circuit impairment dur

40 trocyte-derived E2 in reactive astrogliosis, microglial activation, and neuroprotection following an

41 f neuronal mitochondria in the regulation of microglial activation, and propose neuronal Mfn2 as a li

42 n in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses

43 pyroptosis, as well as resistance to chronic microglial activation, myelin breakdown, hippocampal neu

44 d reactive astrogliosis, as well as enhanced microglial activation, neuronal damage, and cognitive dy

45 Pten in microglia has an etiological role in microglial activation, phagocytosis, and synaptic prunin

46 s confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment

47 observed differential expression related to microglial activation, which is important for synaptic p

48 Several microglial activation-associated and PNS macrophage-enri

49 if such asymmetries have an association with microglial activation.

50 IRF4 regulatory axis is a key determinant in microglial activation.

51 largely unexplored, unlike those that drive microglial activation.

52 sing [(11)C]PK11195 PET imaging, a marker of microglial activation.

53 ity in Pten(m3m4/m3m4) microglia, indicating microglial activation.

54 increases in cocaine self-administration and microglial activation.

55 Da translocator protein (TSPO) PET scans for microglial activation.

56 ich produce neuroinflammation, partly due to microglial activation.

57 rradiated brain ameliorated RICD and reduced microglial activation.

58 nstitutively produced by neurons to suppress microglial activation.

59 ubiquitination, and a consequent decrease of microglial activation.

60 his TLQP21-mediated mechanism might regulate microglial activity in health and disease.

61 of Abeta into dense plaques is a protective microglial activity, limiting the exposure of neurons to

62 s in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.

63 hat genetic variants of AD are enriched in a microglial AD-associated module and identify key transcr

64 es various aspects of brain health including microglial and astrocyte activation.

65 xerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppress

66 tent and durable suppression of HIV in human microglial and monocytic cell lines.

67 IFN pathways, which have been implicated in microglial-associated neuroinflammation and chronic neur

68 t neuronal activity bidirectionally balances microglial association with neuronal cell bodies and mye

69 er injury and in disease may directly affect microglial, astrocyte and oligodendrocyte function, sugg

70 croglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP;

71 Finally, disruption of microglial autophagy in mice expressing human alpha-synu

72 of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals wi

73 Likewise, stiff substrates induce microglial bipolarization and diminish TGFbeta1 expressi

74 Both microglial bipolarization in vivo and the responses to s

75 ayer of high stiffness, which coincides with microglial bipolarization, reduction in TGFbeta1 signali

76 al burden, the IL-10 + M3 group showed lower microglial burden, suggesting that M3 can successfully l

77 Further, while IL-10 expression increased microglial burden, the IL-10 + M3 group showed lower mic

78 Microglial calcium signaling underlies a number of key p

79 the deubiquitination machinery of the human microglial cell (CHME3).

80 ake and clearance of amyloid beta (Abeta) in microglial cell cultures.

81 To test this hypothesis, we determined microglial cell densities (the inverse of cell size) usi

82 was significantly associated with increased microglial cell density.

83 sion induced by EP2 receptor activation in a microglial cell line, reinforcing the use of EP2 antagon

84 ng in turn that the volume monitored by each microglial cell remains constant across mammals.

85 As a consequence, we find that one microglial cell services as few as one and as many as 10

86 Rare sequence variants in the microglial cell surface receptor TREM2 have been shown t

87 both induced and basal HIV transcription in microglial cells (HC69) and monocytic cell lines (U1 and

88 ng USP33 and downstream ATF3 levels in human microglial cells and contributes in neuroinflammation wi

89 The activation of microglial cells and infiltration of Th1 cells resulted

90 neuronal IFNbeta, which, in turn, activates microglial cells and subsequently manifests the infiltra

91 P2Y1/P2Y13 receptors.SIGNIFICANCE STATEMENT Microglial cells are brain-resident immune cells with mu

92 Microglial cells are considered as sensors of brain path

93 probe, for analyzing the metabolome of live microglial cells by drift-tube ion mobility spectrometry

94 We found that microglial cells constitute ~7% of non-neuronal cells in

95 were effectively applied to FACS analysis of microglial cells derived from a mouse model relevant to

96 ssion of sialic acid, are required in murine microglial cells for efficient reovirus binding and infe

97 lead to new strategies to selectively target microglial cells for oncolytic applications.

98 CD33 is upregulated on microglial cells from post-mortem AD patient brains, and

99 Studying microglial cells in acute brain slices, we found that TL

100 cortex indicated a potential involvement of microglial cells in contributing to the structural and f

101 We find that microglial cells occur in similar densities in the brain

102 high neuronal densities and therefore fewer microglial cells per neuron.

103 Microglial cells play essential volume-related actions i

104 This work elucidates host genes that render microglial cells susceptible to reovirus infection and e

105 ds current understanding of the receptors on microglial cells that are engaged by reovirus.

106 d activation and polarization of the primary microglial cells to inflammatory M1 phenotype with the s

107 We thus conclude that the addition of microglial cells to mammalian brains is governed by mech

108 These EVs get internalized by human microglial cells, and miR-148a suppresses the ubiquitin-

109 ll surface and mediate reovirus infection of microglial cells.

110 alic acid-binding receptor on the surface of microglial cells.

111 these cells and consequently rescue critical microglial cellular function such as beta-Amyloid phagoc

112 to circulation-derived monocytes, other non-microglial central nervous system (CNS) macrophage subty

113 s IL-6 and IL-4, and increased expression of microglial chemokines, such as macrophage-colony-stimula

114 p a human pluripotent stem cell (hPSC)-based microglial chimeric mouse brain model by transplanting h

115 Single-cell RNA-sequencing of the microglial chimeric mouse brains reveals that xenografte

116 tility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the

117 Microglial clustering around plaques was impaired, plaqu

118 knockdown of these genes in primary neuronal-microglial cocultures from KCNH2-3.1 mice impairs synaps

119 sm by which vascular interactions facilitate microglial colonization of the brain to later regulate n

120 Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling

121 ast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion o

122 nuclein (alphaSynAgg) stimulation in primary microglial cultures and animal models of PD, as well as

123 lating inflammatory monocytes, did not clear microglial debris.

124 file, and extended their processes to engulf microglial debris.

125 To identify compounds that can reverse microglial defects in Grn-deficient mouse microglia, we

126 ta from SL/vulnerable rats, there was higher microglial density and IL-1beta expression in the vHPC,

127 translation in both sexes, it only increases microglial density and size in males, accompanied by mic

128 nd this work has been greatly facilitated by microglial depletion paradigms.

129 Microglial depletion reduces the odor responses of devel

130 We review the major methods of microglial depletion, including toxin-based, genetic, an

131 ffects were observed in the absence of overt microglial depletion, suggesting that targeting CSF1R si

132 Noise-induced microglial deramification was observed in C57BL/6 mice,

133 ree recent-onset patients may imply impaired microglial development and/or function, which is counter

134 n which perturbed photoreceptor states cause microglial dominant migration to the subretinal space as

135 However, the mechanism of Abeta-induced microglial dysfunction and redox-regulation of microglio

136 Human genetic data indicate that microglial dysfunction contributes to the pathology of A

137 Although microglial eIF4E overexpression elevates translation in

138 onal nets was also evident in R6/2 mice, and microglial elimination not only prevented this but also

139 P(M) mice demonstrated that diazepam limited microglial engulfment of neuronal elements and blocked C

140 to increased synapses as a result of reduced microglial engulfment of PS(+) presynaptic inputs.

141 reduced cortical synapse density, increased microglial engulfment of synapses and altered mouse beha

142 nhibitor Crry at C3-bound synapses decreased microglial engulfment of synapses and protected visual f

143 Active microglial engulfment of synapses regulates brain develo

144 We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM)

145 Our previous study found microglial expression of interferon regulatory factor 5

146 These findings have ramifications for microglial focussed-treatments in AD.

147 ate a novel mechanism by which PS1 modulates microglial function and contributes to Alzheimer's -asso

148 aimed to elucidate whether N1 could modulate microglial function and, if so, determine the consequenc

149 This and other approaches to modify microglial function are a topic of intensive study and p

150 be particularly useful for future studies of microglial function in development and disease.

151 candidates for future studies investigating microglial function in health and disease.

152 oglia-astrocyte cross talk and juxtavascular microglial function in the healthy and diseased brain.

153 cuss the potential implications of origin on microglial function, with particular focus on existing a

154 f synaptic gene expression and modulation of microglial functionality.

155 els have implicated specific Trem2-dependent microglial functions in AD, the underlying molecular mec

156 The effect of TLQP21 on microglial functions in health or disease is not known.

157 se microglia, but our understanding of human microglial functions is largely limited by an inability

158 fore, PLCgamma2 activity regulates divergent microglial functions via distinct TREM2-dependent and -i

159 s, but the mechanisms controlling pathogenic microglial gene expression remain poorly understood.

160 Here we show that MIA alters microglial gene expression with upregulation of cellular

161 on, we observed an enrichment of upregulated microglial genes, but this was not due to neuroinflammat

162 on studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly incre

163 Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lowe

164 ice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intesti

165 Here, we show that microglial GPR56 maintains appropriate synaptic numbers

166 d- and isoform-specific mechanism underlying microglial GPR56-mediated synapse pruning in the context

167 The extent of microglial heterogeneity in humans remains a central yet

168 without CSF1R signaling and reestablish the microglial homeostatic population after CSF1R signaling

169 hPSC-derived microglia largely retain human microglial identity, as they exhibit signature gene expr

170 cing, and highlight the critical role of non-microglial IL-10 in preventing deleterious microglia hyp

171 discover that the microglial IL-10 receptor counteracts the pro-inflammato

172 Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasti

173 al alcohol exposure because of activation of microglial immune cells in the brain.

174 pressed by microglia in the brain, modulates microglial immune homeostasis.

175 uncovered previously unappreciated roles for microglial immunometabolism in shaping neuroinflammation

176 dicating that astrocytes stand by in case of microglial impairment.

177 Conditional knockout of TAK1 in microglial/infiltrated macrophages and neuronal lineages

178 basal forebrain might remove a key check on microglial inflammation induced by amyloid and tau accum

179 active astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later exten

180 dels of PD, suggesting that targeting of the microglial inflammatory response may result in neuroprot

181 quire intracellular adaptor Kindlin3 but not microglial integrins.

182 Here, we review the literature of microglial involvement in ALS and discuss the evidence f

183 ocytic (glial fibrillary acidic protein) and microglial (ionized calcium-binding adapter molecule 1)

184 ity of neuronal mitochondria was linked with microglial junction formation, which was induced rapidly

185 Here, we demonstrated that microglial Kv1.3, a voltage-gated potassium channel, was

186 lation and posttranslational modification of microglial Kv1.3.

187 ediates myelin phagocytosis, but its role in microglial lipid metabolism is unknown.

188 ity of exposed PS using Annexin V or through microglial loss of TREM2.

189 tin Carboxy-terminal Hydrolase L1 [UCH-L1]), microglial/macrophage activation (Ionized calcium bindin

190 Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this pr

191 al demyelinated lesions with axonal loss and microglial/macrophage activation were also observed.

192 l visualization and eliciting a mild chronic microglial/macrophage inflammatory response.

193 asured protein and mRNA levels of a panel of microglial markers across four different brain regions (

194 We investigated association of microglial markers at time of diagnostic lumbar puncture

195 ges and not peripheral myeloid cells acquire microglial markers, indicating that the CNS niche may in

196 aditionally believed if chronic and evolving microglial-mediated neuroinflammation can be inhibited o

197 Microglial-mediated neuroinflammation is induced after s

198 sents a neuronal "eat-me" signal involved in microglial-mediated pruning.

199 during established developmental periods of microglial-mediated synapse elimination.

200 s, and this was linked with restructuring of microglial membrane composition to include a higher GM1

201 tudies revealed an association with impaired microglial metabolic fitness.

202 We investigated the role of TREM2 on the microglial metabolic function in human patient iPSC-deri

203 edonic behaviors in female mice, and altered microglial metabolic reprogramming.

204 Using CellTrace-labeled human GBM and microglial (MG) cells, we established a 2D co-culture in

205 mice resulted in reduced TNF production and microglial MHC-II and improved neurocognitive activity.

206 We show in mice that microglial microRNA expression differs in males and fema

207 ated by microRNAs, but it is unknown whether microglial microRNAs have sex-specific influences on dis

208 These findings suggest that microglial microRNAs influence tau pathogenesis in a sex

209 1/Cdc42-GTPase activator, partially enhances microglial migration in response to oligomeric Abeta(42)

210 Our study shows that the dysfunction of microglial migration in the AD-associated TREM2 R47H var

211 ation of this signaling ameliorates impaired microglial migration response to Abeta(42) , suggesting

212 e, we confirm that TREM2 mutation attenuates microglial migration.

213 cyte endfeet, and the developmental shift in microglial migratory behavior along vessels corresponded

214 Non-microglial mononuclear phagocytes, such as CNS-associate

215 activation has not previously been linked to microglial morphological changes.

216 ne has dichotomous, age-dependent effects on microglial morphology and immune transcript profiles.

217 Microglial morphology and inflammatory cytokine expressi

218 sease, overt inflammation was not evident by microglial morphology or cytokine transcript levels in R

219 ynaptic plasticity, dendritic spine density, microglial morphology, and brain mitochondrial function

220 Thus, microglial mTOR activation represents a novel antiepilep

221 We found that activation of microglial mTOR is antiepileptogenic.

222 These findings suggest that microglial mTOR plays a protective role in mitigating ne

223 To determine the role of microglial mTOR signaling in excitatory injury and epile

224 More importantly, microglial mTOR-deficient mice displayed increased neuro

225 junctions triggered P2Y12 receptor-dependent microglial neuroprotection, regulating neuronal calcium

226 with donor wild-type CSF1R to repopulate the microglial niche.

227 characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleu

228 Immunohistochemical analysis revealed microglial or macrophage infiltration, suggesting activa

229 dies revealed that these MAC2+ cells were of microglial origin.

230 han amyloid plaque load, suggesting that the microglial packing of Abeta into dense plaque is an impo

231 uestion, which cells remove cell debris when microglial phagocytic activity is impaired.

232 The microglial phagocytic activity toward Abeta was restored

233 in the expression of cytokines which promote microglial phagocytic states, such as IL-6 and IL-4, and

234 he impact of established AD risk variants on microglial phagocytosis and debris processing via the en

235 REV-ERBalpha deletion increased microglial phagocytosis of synapses and synapse loss in

236 pression of genes that play crucial roles in microglial phagocytosis.

237 0f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD.

238 Regulation of microglial phenotype by immune receptors has become a ce

239 This is linked to an inflammatory microglial phenotype in the offspring induced by materna

240 netic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery.

241 appaB activity promotes an immunosuppressive microglial phenotype.

242 strates that maternal immune insults perturb microglial phenotypes and influence neuronal functions t

243 scuss the spatial and temporal variations in microglial phenotypes that are observed under different

244 ated neuronal induction of IFNbeta, switched microglial polarization to M2 phenotype, prevented Th1 i

245 s and that metabolic reprogramming regulates microglial polarization, thereby impacting pathological

246 sodeoxycholic acid (TUDCA), on astrocyte and microglial polarization.

247 analysis, we characterized the heterogeneous microglial populations under CSF1R inhibition, including

248 Ia Gq DREADD activation) triggered increased microglial process calcium signaling, often concomitant

249 CaMKIIa Gi DREADD activation) also increased microglial process calcium signaling.

250 Moderate damage induced microglial process extension, which was blocked by P2Y12

251 Thus, microglial processes at these junctions could potentiall

252 action site between neuronal cell bodies and microglial processes in mouse and human brain.

253 However, specific microglial profiles in rat remain elusive due to tedious

254 ition, and shared striking similarities with microglial progenitors in the yolk sac and immature micr

255 Additionally, when combined with microglial proinflammatory cytokines, these exosomes fur

256 Microglial proliferation is regulated by many factors, b

257 ATP triggers the recruitment of microglial protrusions and is converted by the microglia

258 triking loss of synapses driven by excessive microglial pruning early in demyelinating disease, which

259 The molecular mechanisms that restore microglial quiescence after acute stimulation remain lar

260 atory effects of TNF to allow restoration of microglial quiescence after peripheral endotoxin challen

261 and CD68 immunostaining revealed attenuated microglial reactivity in PS19-TREM2R47H versus PS19-TREM

262 gic neuromodulation may remove key checks on microglial reactivity to amyloid and tau.

263 ted animals and also regulated astrocyte and microglial reactivity.

264 re, early intervention downregulated several microglial receptor transcripts (e.g. CD11c, CD47 and CD

265 Because of the specificity and robustness of microglial recombination with P2ry12-CreER, we believe t

266 itor was withdrawn 1-week later to allow for microglial repopulation.

267 gton's disease is associated with a reactive microglial response and consequent inflammation.

268 This is associated with an altered microglial response and deteriorated outcomes.

269 y, we examined Nox2-derived ROS in mediating microglial response to Abeta peptide 1-42 (Abeta(42)) st

270 cumulation, defective TREM2 function affects microglial response to Abeta plaques, exacerbating tissu

271 immune cell of the brain, express TREM2, and microglial responses are implicated in dementia pathways

272 transmits intracellular signals that sustain microglial responses during Alzheimer's disease.

273 Microglial sensing of ATP, the ensuing microglia-depende

274 Microglial shape varied from ramified to amoeboid cells

275 ith distinct phenotypes, including different microglial shapes.

276 al density and size in males, accompanied by microglial shift from homeostatic to a functional state

277 pted a ramified morphology and expressed the microglial signature genes (Tmem119, P2RY12, and Sall1)

278 advances have enabled the identification of microglial signatures in health and disease, including t

279 A higher microglial soma size-to-process length ratio was observe

280 We find that only a small subset of microglial somata and processes exhibited spontaneous ca

281 we suggest a putative role for miR-21 in the microglial spinal injury response.

282 and might be involved in the transition to a microglial state associated with neurodegenerative disea

283 We confirm the presence of four of these microglial subpopulations histologically and illustrate

284 Microglial surveillance is a key feature of brain physio

285 e model, we find that TREM2 deletion reduces microglial survival, impairs phagocytosis of key substra

286 2(-/Y) mice show increased C3 deposition and microglial synapse engulfment.

287 SRPX2 binds C1q and blocks microglial synapse engulfment.

288 Similar to other neurodegenerative diseases, microglial synaptic engulfment and profound synapse loss

289 This daily variation in microglial synaptic phagocytosis was abrogated by global

290 hibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions.

291 gether, these findings provide evidence that microglial Tak1 in the brain, and particularly the brain

292 hypothesised that neuroinflammation and the microglial TLR2-system may act as a core process at the

293 Synucleinphagy requires the presence of microglial Toll-like receptor 4 (TLR4), which induces tr

294 of the genes encoding C1qa and C3 mitigates microglial toxicity and rescues TDP-43 proteinopathy and

295 ously unappreciated contributions of chronic microglial toxicity to TDP-43 proteinopathy during neuro

296 croRNAs leads to sex-specific changes in the microglial transcriptome and tau pathology.

297 ilar artery (BA) abnormalities, we find that microglial transforming growth factor beta-activated kin

298 to show that progranulin deficiency promotes microglial transition from a homeostatic to a disease-sp

299 wever, druggable targets that could modulate microglial TREM2 surface expression are not known.

300 Microglial triggering receptor expressed on myeloid cell

301 Addition of a microglial tumor necrosis factor (TNF) deficiency rescue