Astrocytic processes: from tripartite synapses to the active milieu

Trends in Neurosciences, Год журнала: 2021, Номер 44(10), С. 781 - 792

Опубликована: Авг. 31, 2021

Язык: Английский

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Beyond Activation: Characterizing Microglial Functional Phenotypes

Cells, Год журнала: 2021, Номер 10(9), С. 2236 - 2236

Опубликована: Авг. 28, 2021

Classically, the following three morphological states of microglia have been defined: ramified, amoeboid and phagocytic. While ramified cells were long regarded as “resting”, phagocytic viewed “activated”. In aged human brains, a fourth, morphologically novel state has described, i.e., dystrophic microglia, which are thought to be senescent cells. Since not replenished by blood-borne mononuclear under physiological circumstances, they seem an “expiration date” limiting their capacity phagocytose support neurons. Identifying factors that drive microglial aging may thus helpful delay onset neurodegenerative diseases, such Alzheimer’s disease (AD). Recent progress in single-cell deep sequencing methods allowed for more refined differentiation revealed regional-, age- sex-dependent differences population, growing number studies demonstrate various expression profiles defining subpopulations. Given heterogeneity pathologic central nervous system, need accurately describing morphology patterns becomes increasingly important. Here, we review commonly used markers fluctuations health disease, with focus on IBA1 low/negative can found individuals liver disease.

Язык: Английский

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Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

Frontiers in Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Фев. 16, 2022

Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood-brain barrier maintenance synaptic support. Evidence has emerged from experimental models of glial communication that microglia influence coordinate each other their effects on brain environment. However, due difference cells between humans rodents, it is confirm relevance these findings human brains. Here, we aim review current knowledge microglia-astrocyte crosstalk humans, exploring novel methodological techniques used health disease conditions. This will include an in-depth look at cell culture iPSCs,

Язык: Английский

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The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review

Frontiers in Immunology, Год журнала: 2023, Номер 13

Опубликована: Фев. 2, 2023

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.

Язык: Английский

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Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress

Journal of Ethnopharmacology, Год журнала: 2023, Номер 316, С. 116729 - 116729

Опубликована: Июнь 3, 2023

Язык: Английский

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Reduced secretion of LCN2 (lipocalin 2) from reactive astrocytes through autophagic and proteasomal regulation alleviates inflammatory stress and neuronal damage

Autophagy, Год журнала: 2023, Номер 19(8), С. 2296 - 2317

Опубликована: Фев. 14, 2023

LCN2/neutrophil gelatinase-associated lipocalin/24p3 (lipocalin 2) is a secretory protein that acts as mammalian bacteriostatic molecule. Under neuroinflammatory stress conditions, LCN2 produced and secreted by activated microglia reactive astrocytes, resulting in neuronal apoptosis. However, it remains largely unknown whether inflammatory loss can be minimized modulating production secretion. Here, we first demonstrated was from which were stimulated treatment with lipopolysaccharide (LPS) an stressor. Notably, found two effective conditions led to the reduction of induced levels astrocytes: proteasome inhibition macroautophagic/autophagic flux activation. Mechanistically, suppresses NFKB/NF-κB activation through NFKBIA/IκBα stabilization primary even under downregulation Lcn2 expression. In contrast, autophagic via MTOR reduced intracellular its pre-secretory degradation. addition, N-terminal signal peptide critical for secretion degradation, suggesting these pathways may mechanistically coupled. Finally, observed LPS-induced astrocyte-cultured medium above-mentioned increased viability, stress.Abbreviations: ACM, astrocyte-conditioned medium; ALP, autophagy-lysosome pathway; BAF, bafilomycin A1; BTZ, bortezomib; CHX, cycloheximide; CNS, central nervous system; ER, endoplasmic reticulum; GFAP, glial fibrillary acidic protein; GFP, green fluorescent JAK, Janus kinase; KD, knockdown; LCN2, lipocalin 2; LPS, lipopolysaccharide; MACS, magnetic-activated cell sorting; MAP1LC3/LC3, microtubule-associated 1 light chain 3; MTOR, mechanistic target rapamycin NFKB/NF-κB, nuclear factor kappa polypeptide gene enhancer B cells 1, p105; NFKBIA/IκBα, inhibitor, alpha; OVEX, overexpression; SLC22A17, solute carrier family 22 member 17; SP, peptide; SQSTM1, sequestosome 1; STAT3, transducer activator transcription TNF/TNF-α, tumor necrosis factor; TUBA, tubulin, TUBB3/β3-TUB, beta 3 class III; UB, ubiquitin; UPS, ubiquitin-proteasome system

Язык: Английский

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Modulating the polarization phenotype of microglia – A valuable strategy for central nervous system diseases

Ageing Research Reviews, Год журнала: 2023, Номер 93, С. 102160 - 102160

Опубликована: Дек. 7, 2023

Язык: Английский

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Tuning neural circuits and behaviors by microglia in the adult brain

Trends in Neurosciences, Год журнала: 2024, Номер 47(3), С. 181 - 194

Опубликована: Янв. 21, 2024

Язык: Английский

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Microglia maintain structural integrity during fetal brain morphogenesis

Cell, Год журнала: 2024, Номер 187(4), С. 962 - 980.e19

Опубликована: Фев. 1, 2024

Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display large heterogeneity distribution transcriptomic states, their functions remain poorly characterized. Here, we uncovered role for maintenance structural integrity at two fetal cortical boundaries. At these boundaries between structures that grow distinct directions, accumulate, state resembling post-natal axon-tract-associated microglia (ATM) prevent progression microcavities into cavitary lesions, part mechanism involving ATM-factor Spp1. Spp1 furthermore contribute to rapid repair collectively highlighting protective preserve brain from physiological morphogenetic stress injury. Our study thus highlights key maintaining during morphogenesis, with implications our understanding development.

Язык: Английский

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Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids

Molecular Psychiatry, Год журнала: 2024, Номер 29(8), С. 2424 - 2437

Опубликована: Март 18, 2024

Язык: Английский

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