Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage DOI Creative Commons
Fan Zhang,

Jian Zhou,

Peng Lü

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 30, 2024

Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation substantial amounts lactate to maintain energy demand for neurons and other brain cells. Lactate has garnered increasing attention recent years because its emerging role critical biological processes such as inflammation regulation neuroprotection, particularly through histone lactylation. Bromodomain-containing protein 4 (BRD4) plays crucial maintaining neural development promoting memory formation central nervous system. Nonetheless, function regulatory mechanism BRD4 lactylation following SAH remain elusive. Our findings indicate that BRD4, epigenetic regulator, definitive Both vitro vivo, these results demonstrated targeted silencing can significantly reduce H4K8la lactylation, thereby aggravating A1 polarization ultimately affecting recovery prognosis mice after SAH. In summary, pivotal modulating astrocyte via Targeting this might offer an efficient therapeutic strategy

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

255
Astrocyte metabolism and signaling pathways in the CNS DOI Creative Commons
Yong-Mei Zhang, Yingbei Qi,

Ya-nan Gao

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

Citations

47
Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis DOI Creative Commons
Anne H. Cross, Jeffrey M. Gelfand, Simon Thebault

et al.

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(4), P. 373 - 373

Published: March 11, 2024

Importance Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible that most closely reflects central nervous system biology. Objective To identify CSF biological measures associated with MS pathobiology. Design, Setting, and Participants This cohort study assessed data 2 prospective cohorts: a test provided serial CSF, clinical, imaging assessments multicenter of patients (RMS) or primary (PPMS) who were initiating anti-CD20 treatment (recruitment: 2016-2018; analysis: 2020-2023). A single-site confirmation was used to assess at baseline long-term (>10 year) clinical follow-up (analysis: 2022-2023). Exposures Test-cohort participants initiated standard-of-care ocrelizumab treatment. Confirmation-cohort untreated received disease-modifying therapies. Main Outcomes Measures Twenty-five markers, including neurofilament light chain, heavy glial fibrillary acid protein (GFAP); 24-week confirmed disability progression (CDP24); brain magnetic resonance reflecting focal injury, tissue loss, (slowly expanding lesions [SELs]). Results The (n = 131) included 100 RMS (mean [SD] age, 36.6 [10.4] years; 68 [68%] female 32 [32%] male; Expanded Disability Status Scale [EDSS] score, 0-5.5), 31 PPMS 44.9 [7.4] 15 [48%] 16 [52%] EDSS 3.0-6.5). 68) 41 27 enrolled diagnosis (age, 40 years [range, 20-61 years]; 47 [69%] 21 [31%] male). In the cohort, GFAP correlated SEL count ( r 0.33), greater proportion T2 lesion volume SELs 0.24), lower T1-weighted intensity within –0.33) but not acute inflammatory measures. Neurofilament chain 0.25) –0.28). Immune markers inflammation and, unlike GFAP, impacted by anti-CD20. higher levels CDP24 (hazard ratio, 2.1; 95% CI, 1.3-3.4; P .002). Conclusions Relevance this study, activated (in particular GFAP) specifically outcomes (independent activity). Elevated progression.

Language: Английский

Citations

44
A molecular switch for neuroprotective astrocyte reactivity DOI
Evan G. Cameron, Michael Nahmou, Anna B. Toth

et al.

Nature, Journal Year: 2023, Volume and Issue: 626(7999), P. 574 - 582

Published: Dec. 12, 2023

Language: Английский

Citations

43
Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders DOI

Ailian Wang,

Chen Chen,

Mei Chen

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(2), P. 219 - 234

Published: Jan. 22, 2024

Language: Английский

Citations

27
Obesity-induced inflammation: connecting the periphery to the brain DOI
Ophélia Le Thuc, Cristina García‐Cáceres

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(7), P. 1237 - 1252

Published: July 12, 2024

Language: Английский

Citations

23
Unveiling the role of astrocytes in postoperative cognitive dysfunction DOI
Liang He,

X. Duan,

Shikuo Li

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102223 - 102223

Published: Feb. 5, 2024

Language: Английский

Citations

20
Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping DOI Creative Commons
Di Zhang, Leslie A. Kirby, Yingxin Lin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 28, 2024

Abstract The ability to spatially map multiple layers of the omics information over different time points allows for exploring mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC–RNA–Protein-seq) CTRP-seq CUT&Tag– RNA–Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) dynamic remodeling development neuroinflammation. A spatiotemporal atlas mouse was obtained at stages from postnatal day P0 P21, compared regions interest human developing brains. Specifically, cortical area, discovered temporal persistence spreading chromatin accessibility layer-defining transcription factors. In corpus callosum, observed priming myelin genes across subregions. Together, it suggests a role layer specific projection neurons coordinate axonogenesis myelination. We further mapped lysolecithin (LPC) neuroinflammation model common molecular programs Microglia, exhibiting both conserved distinct inflammation resolution, are transiently activated not only core LPC lesion, but also distal locations presumably through neuronal circuitry. Thus, this work unveiled differential neuroinflammation, resulting valuable data resource investigate function

Language: Английский

Citations

17
From Homeostasis to Neuroinflammation: Insights into Cellular and Molecular Interactions and Network Dynamics DOI Creative Commons

Ludmila Müller,

Svetlana Di Benedetto,

Viktor Müller

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(1), P. 54 - 54

Published: Jan. 5, 2025

Neuroinflammation is a complex and multifaceted process that involves dynamic interactions among various cellular molecular components. This sophisticated interplay supports both environmental adaptability system resilience in the central nervous (CNS) but may be disrupted during neuroinflammation. In this article, we first characterize key players neuroimmune interactions, including microglia, astrocytes, neurons, immune cells, essential signaling molecules such as cytokines, neurotransmitters, extracellular matrix (ECM) components, neurotrophic factors. Under homeostatic conditions, these elements promote cooperation stability, whereas neuroinflammatory states, they drive adaptive responses become pathological if dysregulated. We examine how mediated through actors pathways, create networks regulate CNS functionality respond to injury or inflammation. To further elucidate dynamics, provide insights using multilayer network (MLN) approach, highlighting interconnected nature of under inflammatory conditions. perspective aims enhance our understanding communication mechanisms underlying shifts from homeostasis Applying an MLN approach offers more integrative view adaptability, helping clarify processes identify novel intervention points within layered landscape responses.

Language: Английский

Citations

4
Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia–astrocyte communication in Alzheimer's disease DOI Creative Commons

Ze‐Hu Sheng,

Linlin Wang, Ming Chen

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 2, 2025

Cerebrospinal fluid (CSF) β2-microglobulin (β2M) has been demonstrated as an important factor in β-amyloid (Aβ) neurotoxicity and a potential target for Alzheimer's disease (AD). However, more investigation is required to ascertain the relationship between β2M glial activities AD pathogenesis. In this study, 211 participants from Neuroimaging Initiative (ADNI) with CSF Plasma β2M, fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), Aβ42, phosphorylated-tau (P-tau) total tau (T-tau) were divided into four groups, stage 0, 1, 2, suspected non-AD pathology (SNAP) based National Institute Aging- Association (NIA-AA) criteria. Multiple linear regression, mixed effects models, causal mediation analyses bootstrapped 10,000 iterations used investigate underlying associations among biomarkers at baseline during longitudinal visit. concentration decreased amyloid 1 compared 0 increased neurodegeneration SNAP 1. Moreover, level was positively correlated Aβ42 (β = 0.230), P-tau 0.564), T-tau 0.603), GFAP 0.552), sTREM2 0.641) (all P < 0.001). only longitudinally change. The correlation of (proportion 25.4%, 0.001) 26.7%, partially mediated by participants, reproduced late-life individuals. Furthermore, astrocyte cascade also pathological (β2M → YKL-40 P-tau/T-tau, IE: 0.424—0.435, all Nevertheless, not significant. Additionally, there no association plasma biomarkers. dynamic associated neuroinflammation. might mediate pathology, complementing existing research effect providing new perspective treatment.

Language: Английский

Citations

2