Cytokine relay from the peripheral to the central: Secrets behind fever DOI Open Access
Xianshu Bai

Acta Physiologica, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Fever is often triggered by infections or inflammatory conditions, primarily mediated the immune system. Immune cells like macrophages and dendritic detect pathogens through pathogen-associated molecular patterns, such as lipopolysaccharides (LPS).1 In response, these release a significant number of factors cytokines, which travel bloodstream to hypothalamus, body's thermoregulatory center. Once in cytokines stimulate various cells, including microglia—the innate cell central nervous system.2 This stimulation initiates complex cascade that raises body temperature. However, precise mechanisms hypothalamic microglia interact with peripheral induce fever remain unclear.3 this issue Acta Physiologica, Yu et al. elucidate driven interactions between preoptic anterior hypothalamus (POAH) microglia.4 study, they administered 20 μg/kg LPS via tail vein, characteristic biphasic at 2 6 hours post-injection (hpi). At each time point, levels key pro-inflammatory involved development, IL-1β, IL-18, interferon (IFN)-β, TNF-α, were measured. hpi, there was slight but not increase blood serum. both CNS microglia, accompanied dramatic rise PGE2 IL-1β POAH region. Importantly, due entering brain, neither Evans blue nor FITC-LPS applied peripherally detected indicating activation direct result exposure. As sets are mainly expressed authors hypothesized entry derived from macrophages. To further investigate, selectively depleted administering clodronate-liposome tail-vein injection 24 h before treatment. absence macrophages, even after injection, temperature changed. Depleting also suppressed LPS-induced cytokine serum region, suggesting play role development. Conversely, when using same drug injected directly into similarly elevated remained low PO/AH region Although significantly reduced comparison LPS-treated control mice, it slightly higher than healthy likely remaining action macrophage-derived POAH. Using bulk RNA-sequencing, identified genes associated NOD-like receptor signaling pathway, particularly Caspase11-NLRP3 inflammasome, hpi LPS, especially microglia. These observations suggest first phase (2 injection) may be attributed effect while second peak amplification within data support hypothesis relay mechanism vitro co-culture experiments revealed activated bone marrow-derived (BMDM) BV-2 co-cultured BMDM upregulate cytokines. addition, increased Caspase11 expression. observed treated conditioned medium amplified system incubated 39°C, mimicking high suggests microglial contributing By silencing microglia-specific Caspase11, able suppress without affecting first, expression returned levels. overexpressing elevated. The study advances our understanding underlying identifying player driving non-canonical inflammasome pathway. intricate cooperation body, involving periphery CNS, great interest, could lead new therapeutic approaches for managing clinical settings. future, studies needed determine whether act on other populations. Endothelial lining brain vessels respond produce PGE2, facilitating response.5 A recent demonstrated triggers an adenosine, acts astrocytes modulates reactivity systemically induced sepsis model.6 Oligodendrocyte precursor some locate vessels,7 can cells8, 9 participate modulation.10 Therefore, remains studied whether, apart glial fever. It unclear how microglia-derived modulate fever, either interacting oligodendrocytes.11 Additionally, detailed investigations required clarify interaction involves indirect mechanisms. For instance, tracing (using Rosa26-methionyl tRNA synthetase reporter) would promising starting point. Xianshu Bai: Writing – original draft; conceptualization. work supported grants Deutsche Forschungsgemeinschaft (DFG BA 8014/1-1), Deutscher Akademischer Austauschdienst DAAD (57598458), Rolf M. Schwiete Stiftung 2023, University Saarland (Anschubfinanzierung2024, HOMFORexzellent2018 NanoBioMed Young Investigator grant 2021). Data sharing applicable article no created analyzed study.

Language: Английский

The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation DOI Creative Commons
Srishti Kala, Andrew G. Strutz, Moriah E. Katt

et al.

Neurology International, Journal Year: 2025, Volume and Issue: 17(1), P. 6 - 6

Published: Jan. 13, 2025

Neuroinflammation is a blanket term that describes the body’s complex inflammatory response in central nervous system (CNS). It encompasses phenotype shift to proinflammatory state, release of cytokines, recruitment peripheral immune cells, and wide variety other processes. has been implicated nearly every major CNS disease ranging from Alzheimer’s brain cancer. Understanding modeling neuroinflammation critical for identification novel therapeutic targets treatment diseases. Unfortunately, translation findings non-human models left much be desired. This review systematically discusses role human pluripotent stem cell (hPSC)-derived glia supporting cells within CNS, including astrocytes, microglia, oligodendrocyte precursor pericytes, endothelial describe state field hope future discoveries. hPSC-derived offer an expanded potential study pathobiology immunomodulatory cascades impact progression. While progress made development models, there explore application these understand CNS.

Language: Английский

Citations

0
Interactions of Oligodendrocyte Precursor Cells and Dopaminergic Neurons in the Mouse Substantia Nigra DOI Creative Commons
Julia C. Fitzgerald, Kuan‐Pin Su,

Frederek Reinecke

et al.

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(1)

Published: Jan. 1, 2025

ABSTRACT Parkinson's disease (PD) is a prevalent neurodegenerative caused by the death of dopaminergic neurons within substantia nigra pars compacta (SNpc) region midbrain. Recent genomic and single cell sequencing data identified oligodendrocytes oligodendrocyte precursor cells (OPCs) to confer genetic risk in PD, but their biological role unknown. Although SNpc are scarcely or thinly myelinated, there gap knowledge concerning physiological interactions between oligodendroglia. We sought investigate distribution OPCs with regard myelination state mouse (SN) high‐resolution imaging provide morphological assessment OPC‐dopaminergic neuron quantification numbers across different age groups. evenly distributed midbrain throughout lifespan they physically interact both soma axons neurons. The presence interaction does not correlate myelin. Myelination sparse SNpc, including fibers originating from projecting through reticulata (SNpr). report that exist 1:1 ratio accounting for 15%–16% all This description provides first look at longitudinal mice, suggesting additional functions beyond differentiation into myelinating oligodendrocytes. image

Language: Английский

Citations

0
Cytokine relay from the peripheral to the central: Secrets behind fever DOI Open Access
Xianshu Bai

Acta Physiologica, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Fever is often triggered by infections or inflammatory conditions, primarily mediated the immune system. Immune cells like macrophages and dendritic detect pathogens through pathogen-associated molecular patterns, such as lipopolysaccharides (LPS).1 In response, these release a significant number of factors cytokines, which travel bloodstream to hypothalamus, body's thermoregulatory center. Once in cytokines stimulate various cells, including microglia—the innate cell central nervous system.2 This stimulation initiates complex cascade that raises body temperature. However, precise mechanisms hypothalamic microglia interact with peripheral induce fever remain unclear.3 this issue Acta Physiologica, Yu et al. elucidate driven interactions between preoptic anterior hypothalamus (POAH) microglia.4 study, they administered 20 μg/kg LPS via tail vein, characteristic biphasic at 2 6 hours post-injection (hpi). At each time point, levels key pro-inflammatory involved development, IL-1β, IL-18, interferon (IFN)-β, TNF-α, were measured. hpi, there was slight but not increase blood serum. both CNS microglia, accompanied dramatic rise PGE2 IL-1β POAH region. Importantly, due entering brain, neither Evans blue nor FITC-LPS applied peripherally detected indicating activation direct result exposure. As sets are mainly expressed authors hypothesized entry derived from macrophages. To further investigate, selectively depleted administering clodronate-liposome tail-vein injection 24 h before treatment. absence macrophages, even after injection, temperature changed. Depleting also suppressed LPS-induced cytokine serum region, suggesting play role development. Conversely, when using same drug injected directly into similarly elevated remained low PO/AH region Although significantly reduced comparison LPS-treated control mice, it slightly higher than healthy likely remaining action macrophage-derived POAH. Using bulk RNA-sequencing, identified genes associated NOD-like receptor signaling pathway, particularly Caspase11-NLRP3 inflammasome, hpi LPS, especially microglia. These observations suggest first phase (2 injection) may be attributed effect while second peak amplification within data support hypothesis relay mechanism vitro co-culture experiments revealed activated bone marrow-derived (BMDM) BV-2 co-cultured BMDM upregulate cytokines. addition, increased Caspase11 expression. observed treated conditioned medium amplified system incubated 39°C, mimicking high suggests microglial contributing By silencing microglia-specific Caspase11, able suppress without affecting first, expression returned levels. overexpressing elevated. The study advances our understanding underlying identifying player driving non-canonical inflammasome pathway. intricate cooperation body, involving periphery CNS, great interest, could lead new therapeutic approaches for managing clinical settings. future, studies needed determine whether act on other populations. Endothelial lining brain vessels respond produce PGE2, facilitating response.5 A recent demonstrated triggers an adenosine, acts astrocytes modulates reactivity systemically induced sepsis model.6 Oligodendrocyte precursor some locate vessels,7 can cells8, 9 participate modulation.10 Therefore, remains studied whether, apart glial fever. It unclear how microglia-derived modulate fever, either interacting oligodendrocytes.11 Additionally, detailed investigations required clarify interaction involves indirect mechanisms. For instance, tracing (using Rosa26-methionyl tRNA synthetase reporter) would promising starting point. Xianshu Bai: Writing – original draft; conceptualization. work supported grants Deutsche Forschungsgemeinschaft (DFG BA 8014/1-1), Deutscher Akademischer Austauschdienst DAAD (57598458), Rolf M. Schwiete Stiftung 2023, University Saarland (Anschubfinanzierung2024, HOMFORexzellent2018 NanoBioMed Young Investigator grant 2021). Data sharing applicable article no created analyzed study.

Language: Английский

Citations

1