The effect of Ferroptosis -related Mitochondrial Dysfunction in the Development of Temporal Lobe Epilepsy

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102248 - 102248

Published: Feb. 24, 2024

Language: Английский

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Imbalance in Glucose Metabolism Regulates the Transition of Microglia from Homeostasis to Disease-Associated Microglia Stage 1

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(20), P. e1563232024 - e1563232024

Published: April 2, 2024

Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates first DAM1 transition is unknown. We report that glucose dyshomeostasis inhibits and PKM2 plays a role. As tumors, was aberrantly elevated both male female human AD brains, unlike it expressed active tetramers, well among + surrounding plaques 5XFAD mice. snRNAseq analyses of without Pkm2 mice revealed significant increases markers distinct metabolic cluster, which enriched genes for metabolism, DAM1, risk. incidentally exhibited reduction amyloid pathology microglial . Surprisingly, glycolysis spare respiratory capacity, correlated with restoration mitochondrial cristae alterations. In addition, situ spatial metabolomics plaque-bearing an increase activity. These results together suggest not only glycolytic also inputs are critical to development DAM signatures

Language: Английский

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The impact of neuroinflammation on neuronal integrity

Immunological Reviews, Journal Year: 2024, Volume and Issue: 327(1), P. 8 - 32

Published: Oct. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Language: Английский

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Interaction of Gut-Microbial Amyloids with Endogenous Amyloids can Drives Microglial Hyperactivity and Neuroinflammation in Alzheimer’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Gut bacteria have emerged as silent drivers in the pathology of Alzheimer’s disease (AD). They also make amyloids with structure analogue to pathological and potential cross-seed propagate a prion-like manner. AD is characterised by accumulation mature extracellular Amyloid-β (Aβ) plaques which are surrounded inflammatory microglia. We report that exposure interspecies microbial FapC (fimbriae) CsgA (curli) from opportunistic gut pathogens Pseudomonas aeruginosa Escherichia coli hyperactivates microglia against Aβ fibrils. Microbial fibrils converge phagocytic compartments through subsequent internalization, not observed alone. This convergence promotes pro-inflammatory defective proteome similar those brains. The resulting clusters develop pro-inflammatory, indigestible interactome eventually regurgitated, inducing progressive degeneration bystander neurons ultimately leading cognitive decline. Collectively, these findings provide compelling evidence can trigger microglia-driven neuroinflammation.

Language: Английский

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Astrocyte-derived complement C3 facilitated microglial phagocytosis of synapses in Staphylococcus aureus-associated neurocognitive deficits

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1013126 - e1013126

Published: April 28, 2025

The presence of pathogens is a significant challenge in causing brain infections and tissue damage. There growing evidence that pathogen are commonly associated with cognitive dysfunction mental health problems, but the underlying mechanisms not yet fully understood. Here, we found microglia astrocyte activation, neuronal damage, synapse loss, impairment Staphylococcus aureus ( S. ) induced mouse model. An unbiased transcription profile isolated derived from -infected mice identified involvement microglial phagosome regulation neurogenesis. Our findings indicate complement C1q C3 upregulated, astroglial release activates to phagocytose synapses. Blocking C3-C3aR axis can improve phagocytosis, thus rescuing loss infected mice. These results induces elimination by activating astrocytes through signaling. This suggests mechanism signaling bridged crosstalk between -associated post-infectious dysfunction, provide potential therapeutic targets for managing pathogen-associated infections.

Language: Английский

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Increased Pan-Type, A1-Type, and A2-Type Astrocyte Activation and Upstream Inflammatory Markers Are Induced by the P2X7 Receptor

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8784 - 8784

Published: Aug. 13, 2024

This study asked whether the P2X7 receptor was necessary and sufficient to trigger astrocyte polarization into neuroinflammatory activation states. Intravitreal injection of agonist BzATP increased gene expression pan-astrocyte markers

Language: Английский

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Metabolic control of microglia in health and disease

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 143 - 159

Published: Jan. 1, 2025

Language: Английский

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Herkinorin ameliorates neuronal damage in a pentylenetetrazol-induced epilepsy rat model through altering microglial and astrocytic activation by inhibiting PARP1 and NF-κB

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114588 - 114588

Published: April 10, 2025

Language: Английский

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Microglial TAK1 promotes neurotoxic astrocytes and cognitive impairment in LPS-induced hippocampal neuroinflammation

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 110225 - 110225

Published: May 1, 2025

The peripheral immune system has a strong effect on the central nervous (CNS). Systemic lipopolysaccharides (LPS) administration triggers robust microglial activation and induces significant inflammatory responses in hippocampus. This study investigates role of Transforming Growth Factor-β-Activated Kinase 1 (TAK1) mediating LPS-induced hippocampal neuroinflammation cognitive impairment. Our findings reveal that LPS TAK1, which turn actives downstream effector NF-κB/p65 to release pro-inflammatory cytokines. activated microglia also promote astrocytes polarize into neurotoxic phenotype (A1-like phenotype), cause loss newborn neurons dentate gyrus (DG). However, TAK1 reduction inhibits responses, limits astrocytes, rescues neurons, subsequently improves deficits, suggesting targeting may be an effective strategy for alleviating neuroinflammation. interaction between activation, transition enhances our understanding cellular dynamics driving neuroinflammation, therapeutic target treating

Language: Английский

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Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure

Environmental Science and Pollution Research, Journal Year: 2024, Volume and Issue: 31(10), P. 15746 - 15758

Published: Feb. 2, 2024

Language: Английский

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