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Article Dans Une Revue Neurobiology of Disease Année : 2023

PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions

Hélène E. Hirbec
Etienne Audinat

Résumé

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 that of the pro-inflammatory biomarkers TNFα, IL-1β, and NF-kB in the epileptogenic hippocampus compared to the adjacent amygdala and temporal cortex. Using an experimental mouse model of MTLE, we found hippocampal Piezo1 and cytokine expression levels increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1β, and Nf-kb expression in the hippocampal foci. Next, by combining RNAscope with immunofluorescence, 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 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 neuro-mechanobiology and neuro-inflammatory cell remodeling. The precise cellular and functional mechanisms regulating this interplay in disease conditions warrant further investigation.
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Dates et versions

hal-04213180 , version 1 (06-10-2023)

Identifiants

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Valentin Garcia, Marine Blaquiere, Alicia Janvier, Noemie Cresto, Carla Lana, et al.. PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions. Neurobiology of Disease, 2023, pp.106297. ⟨10.1016/j.nbd.2023.106297⟩. ⟨hal-04213180⟩
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