Academic Journal
PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions
| العنوان: | PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions |
|---|---|
| المؤلفون: | Valentin Garcia, Marine Blaquiere, Alicia Janvier, Noemie Cresto, Carla Lana, Athenais Genin, Helene Hirbec, Etienne Audinat, Adele Faucherre, Emmanuel L. Barbier, Sophie Hamelin, Philippe Kahane, Chris Jopling, Nicola Marchi |
| المصدر: | Neurobiology of Disease, Vol 187, Iss , Pp 106297- (2023) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Piezo1, Neuro-inflammation, Neuro-mechanobiology, Focal seizures, Astrocytes, Microglia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: | Mechanosensors are emerging players responding to hemodynamic and physical inputs. Their significance in the central nervous system remains relatively uncharted. Using human-derived brain specimens or cells and a pre-clinical model of mesio-temporal lobe epilepsy (MTLE), we examined how the mRNA levels of the mechanosensitive channel PIEZO1 adjust to disease-associated pro-inflammatory trajectories.In brain tissue micro-punches obtained from 18 drug-resistant MTLE patients, PIEZO1 expression positively correlated with pro-inflammatory biomarkers TNFα, IL-1β, and NF-kB in the epileptogenic hippocampus compared to the adjacent amygdala and temporal cortex tissues. In an experimental MTLE model, hippocampal Piezo1 and cytokine expression levels were increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1β, and Nf-kb in the hippocampal foci. Next, by combining RNAscope with immunohistochemistry, we identified Piezo1 in glio-vascular cells. Post-SE and during epileptogenesis, ameboid IBA1 microglia, hypertrophic GFAP astrocytes, and damaged NG2DsRed pericytes exhibited time-dependent patterns of increased Piezo1 expression. Digital droplet PCR analysis confirmed the Piezo1 trajectory in isolated hippocampal microvessels in the ipsi and contralateral hippocampi. The combined examinations performed in this model showed Piezo1 expression returning towards basal levels after the epileptogenesis-associated peak inflammation. From these associations, we next asked whether pro-inflammatory players directly regulate PIEZO1 expression. We used human-derived brain cells and confirmed that endothelium, astrocytes, and pericytes expressed PIEZO1. Exposure to human recombinant TNFα or IL1β upregulated NF-kB in all cells. Furthermore, TNFα induced PIEZO1 expression in a dose and time-dependent manner, primarily in astrocytes.This exploratory study describes a spatiotemporal dialogue between PIEZO1 brain cell-mechanobiology and neuro-inflammatory cell remodeling. The ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1095-953X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0969996123003121; https://doaj.org/toc/1095-953X; https://doaj.org/article/c1415310d3054dd4ace2dd6dec496b9a |
| DOI: | 10.1016/j.nbd.2023.106297 |
| الاتاحة: | https://doi.org/10.1016/j.nbd.2023.106297 https://doaj.org/article/c1415310d3054dd4ace2dd6dec496b9a |
| رقم الانضمام: | edsbas.67B021A8 |
| قاعدة البيانات: | BASE |
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In an experimental MTLE model, hippocampal Piezo1 and cytokine expression levels were increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1β, and Nf-kb in the hippocampal foci. Next, by combining RNAscope with immunohistochemistry, we identified Piezo1 in glio-vascular cells. Post-SE and during epileptogenesis, ameboid IBA1 microglia, hypertrophic GFAP astrocytes, and damaged NG2DsRed pericytes exhibited time-dependent patterns of increased Piezo1 expression. Digital droplet PCR analysis confirmed the Piezo1 trajectory in isolated hippocampal microvessels in the ipsi and contralateral hippocampi. The combined examinations performed in this model showed Piezo1 expression returning towards basal levels after the epileptogenesis-associated peak inflammation. From these associations, we next asked whether pro-inflammatory players directly regulate PIEZO1 expression. 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