Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling
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PROVIDER: PRJNA1268930 | ENA |
REPOSITORIES: ENA
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Project description:Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling
| PRJNA1061535 | ENA
Project description:Unilateral whisker lesioning at age P4 leads to removal of thalamocortical synapses in layer IV of the barrel cortex over the course of the next 6 days. Synapse removal is mediated by microglia and induced by CX3CL1-CX3CR1 signaling between neurons and microglia. Downstream of CX3CL1-CX3CR1 activation, microglia induce astrocyte morphological changes and activation of canonical Wnt signaling in astrocytes. To explore the spatial pattern of microglia Wnt ligand expression and astrocyte Wnt receptor expression in astrocytes, we analyzed coronal sections containing the barrel cortex from 4 wild-type mice and 4 CX3CL1 knockout mice at 24 hours after whisker lesioning by multiplexed error-robust fluorescent in situ hybridization (MERFISH).
2025-09-10 | GSE298314 | GEO
Project description:Unilateral whisker lesioning at age P4 leads to removal of thalamocortical synapses in layer IV of the barrel cortex over the course of the next 6 days. Synapse removal is mediated by microglia and induced by CX3CL1-CX3CR1 signaling between neurons and microglia. Downstream of CX3CL1-CX3CR1 activation, microglia induce astrocyte morphological changes. To identify molecular crosstalk between astrocytes and microglia, we performed translating ribosome affinty purification followed by RNA sequencing (TRAP-Seq).
2025-08-07 | GSE252628 | GEO
Project description:Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented microglia reactivity and abolished the behavioral phenotype elicited by Meth in the elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
2021-07-22 | GSE180497 | GEO
Project description:This study defines a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus.
2020-07-01 | GSE150712 | GEO
Project description:Genetic studies implicate Clusterin (CLU) in the pathogenesis of Alzheimer’s disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased NfkB-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia dependent modulation of extracellular APOE and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers. By integrating mouse and human cellular models with comprehensive analyses of human plasma and brain tissue, we demonstrate that CLU AD risk alleles are associated with reduced CLU protein and heightened inflammatory profiles. These findings establish a mechanistic link between AD genetic risk factors, astrocyte reactivity, and microglia-mediated effects on synaptic integrity. Collectively, these results support a model in which CLU upregulation in response to neuropathology is associated with maintenance of cognitive function, while diminished astrocyte CLU levels heighten disease susceptibility.
2025-04-28 | GSE294133 | GEO
Project description:Genetic studies implicate Clusterin (CLU) in the pathogenesis of Alzheimer’s disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased NfkB-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia dependent modulation of extracellular APOE and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers. By integrating mouse and human cellular models with comprehensive analyses of human plasma and brain tissue, we demonstrate that CLU AD risk alleles are associated with reduced CLU protein and heightened inflammatory profiles. These findings establish a mechanistic link between AD genetic risk factors, astrocyte reactivity, and microglia-mediated effects on synaptic integrity. Collectively, these results support a model in which CLU upregulation in response to neuropathology is associated with maintenance of cognitive function, while diminished astrocyte CLU levels heighten disease susceptibility.
2025-04-28 | GSE289565 | GEO
Project description:To investigate the influence of Aβ40WT and Aβ42WT fibrils on astrocyte and microglia, we isolated astrocyte and microglia from P2 SD rats and treated glia cells with Aβ40WT and Aβ42WT fibrils for 24 hours. We then performed gene expression profiling analysis using data obtained from RNA-seq of astrocyte and microglia treated with Aβ fibrils.
2022-08-17 | GSE211198 | GEO
Project description:Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.
2018-02-05 | GSE109352 | GEO
Project description:Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.
2018-02-05 | GSE109353 | GEO