Unlabelled: Early life stress (ELS) has lasting consequences on microglia and brain macrophage function. During ELS, microglia and brain macrophages alter their engagement with synapses leading to changes in neuronal excitability. Further, ELS can induce innate immune memory formation in microglia and brain macrophages resulting in altered responsivity to future environmental stimuli. These alterations can result in lasting adaptations in circuit function and may mediate the relationship between ELS and the risk to develop alcohol use disorder (AUD). Whether microglia and brain macrophages truly mediate this relationship remains elusive. Here, we report: 1) an ELS model, psychosocial stress (PSS), increases binge-like ethanol consumption in early adulthood. 2) Repeated binge-like ethanol consumption increases microglia and brain macrophage population densities across the brain. 3) PSS may elicit innate immune memory formation in microglia and brain macrophages leading to altered population densities following repeated binge-like ethanol consumption. 4) Microglia and brain macrophage inhibition trended towards preventing PSS-evoked changes in binge-like ethanol consumption and normalized microglia and brain macrophage population densities. Therefore, our study suggests that acutely inhibiting microglia and brain macrophage function during periods of early life PSS may prevent innate immune memory formation and assist in reducing the risk to develop AUD.
Highlights: An early life psychosocial stress (PSS) exposure increases ethanol consumptionMicroglial inhibition during PSS trends towards reducing ethanol consumptionBinge ethanol consumption increases microglial count and alters cell proximityEarly life PSS alters microglial responsivity to binge ethanol consumptionMicroglial inhibition may prevent microglial innate immune memory formation.
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http://dx.doi.org/10.1101/2024.07.27.605403 | DOI Listing |
Stroke
January 2025
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, United Kingdom.
Background: How cerebral microbleeds (CMBs) are formed, and how they cause tissue damage is not fully understood, but it has been suggested they are associated with inflammation, and they could also be related to increased blood-brain barrier (BBB) leakage. We investigated the relationship of CMBs with inflammation and BBB leakage in cerebral small vessel disease, and in particular, whether these 2 processes were increased in the vicinity of CMBs.
Methods: In 54 patients with sporadic cerebral small vessel disease presenting with lacunar stroke, we simultaneously assessed microglial activation using the positron emission tomography ligand [11C]PK11195 and BBB leakage using dynamic contrast enhanced magnetic resonance imaging, on a positron emission tomography-magnetic resonance imaging system.
Theranostics
January 2025
Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Tianjin Medical University General Hospital, Tianjin 300052, China.
Intracerebral hemorrhage (ICH) is a devastating form of stroke with a lack of effective treatments. Following disease onset, ICH activates microglia and recruits peripheral leukocytes into the perihematomal region to amplify neural injury. Bruton's tyrosine kinase (BTK) controls the proliferation and survival of various myeloid cells and lymphocytes.
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January 2025
State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, China.
White matter has emerged as a key therapeutic target in ischemic stroke due to its role in sensorimotor and cognitive outcomes. Our recent findings have preliminarily revealed a potential link between microglial HDAC3 and white matter injury following stroke. However, the mechanisms by which microglial HDAC3 mediates these effects remain unclear.
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January 2025
Neurooncology Unit, Instituto de Investigación Biomédicas I+12, Hospital Universitario 12 de Octubre, Madrid 28041, Spain.
Glioblastoma IDH wild type (GBM IDH wt) has a poor prognosis and a strongly associated with inflammatory processes. Inflammatory molecules generate positive feedback with tumor cells fueling tumor growth as well as recruitment of immune cells that promote aggressiveness. Although the role of many inflammatory molecules is well known, there are many macromolecules, such as the S100A proteins, whose role is only now beginning to be established.
View Article and Find Full Text PDFFront Aging Neurosci
December 2024
Department of Ophthalmology and Visual Sciences, Faculty of Medicine, Eye Care Centre, The University of British Columbia, Vancouver, BC, Canada.
Introduction: Apolipoprotein E (ApoE) plays a crucial role in lipid homeostasis, predominantly expressed in astrocytes and to a lesser extent in microglia within the central nervous system (CNS). While the allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), its precise role in AD pathogenesis remains elusive. -knockout (-ko) mice, mice expressing human , and human carriers exhibit similar deficits in lipid metabolism, cognitive and behavioral functions, and neurodegeneration.
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