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Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.
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http://dx.doi.org/10.1016/j.neuron.2024.07.015 | DOI Listing |
Neurochem Int
September 2025
Department of Neurobiology, College of Basic Medicine, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University, Shanghai 200433, China. Electronic address:
Traditionally, oligodendrocyte precursor cells (OPCs) were primarily regarded for their differentiation potential to mature oligodendrocytes that ensheath central nervous system (CNS) axons through myelin formation. Recent breakthroughs in single-cell sequencing and in vivo imaging technologies have revolutionized our understanding, revealing that OPCs engage in extensive dynamic interactions with diverse CNS cell populations during neurodevelopment, tissue homeostasis maintenance, and pathological microenvironment remodeling. Notably, while OPCs exhibit relatively conserved phenotypic signatures, their functional plasticity within heterogeneous microenvironments demonstrates significant spatial specificity and disease-context dependence.
View Article and Find Full Text PDFImmunopharmacol Immunotoxicol
September 2025
Neuroscience Research Center, Suleyman Demirel University, Isparta, Türkiye.
Background: Microglia are brain resident cells that control neural network maintenance, damage healing, and brain development. Microglia undergo apoptosis, cytokine production, and reactive free radicals of oxygen (ROS) in response to lipopolysaccharide (LPS) stimulation. TRPM2 is activated by LPS-induced oxidative stress, but it is inhibited by carvacrol (CARV) and N-(p-amylcinnamoyl)anthranilic acid (ACA).
View Article and Find Full Text PDFFront Immunol
September 2025
Max Planck Institute for Human Development, Center for Lifespan Psychology, Berlin, Germany.
Neuroinflammation is a dynamic, context-sensitive process that plays essential roles in brain development, maintenance, and response to injury. It reflects a finely balanced neuroimmune state-facilitating repair and adaptation under homeostatic conditions, while also contributing to dysfunction when dysregulated or chronically activated. In this mini-review, we examine the cellular and molecular mechanisms underlying neuroinflammatory responses, focusing on the roles of microglia and astrocytes, their bidirectional communication with neurons, and their interaction with peripheral immune signals.
View Article and Find Full Text PDFWhile both Primary Age-Related Tauopathy (PART) and Alzheimer's Disease (AD) involve the accumulation of hyperphosphorylated tau (pTau)-positive neurofibrillary tangles (NFTs) in the hippocampus, PART is distinguished by the absence of β-amyloid (Aβ) deposition and is generally associated with milder cognitive impairment than AD. To delineate cellular and molecular mechanisms that are common or uniquely linked to disease progression in PART and AD, we constructed a transcriptome-wide, high-resolution atlas of the human hippocampus using samples from six individuals spanning the aged control (AC), PART, and AD groups. Our results supported that PART represent a precursor stage of AD, as evidenced by the altered transcriptional profiles of excitatory neurons (Exc) in the PART group, which exhibited a markedly increased capacity to promote Aβ production compared to both AC and AD groups.
View Article and Find Full Text PDFJ Neuroimmune Pharmacol
September 2025
Immunoenocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St. 31-343, Kraków, Poland.
Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by hallmark pathologies such as amyloid-beta (Aβ) plaque accumulation, tau hyperphosphorylation, and progressive neuronal dysfunction. While much attention has focused on neurons and microglia, recent studies underscore the significant yet understudied roles of oligodendrocytes (OL) and oligodendrocyte precursor cells (OPC) in AD pathology. OL, responsible for myelin production and maintenance, are impaired early in AD, contributing to demyelination, synaptic dysfunction, and cognitive decline.
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