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

Neurobiol Dis. 2023 Sep 15:106297. doi: 10.1016/j.nbd.2023.106297. Online ahead of print.ABSTRACTMechanosensors 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...
Source: Neurobiology of Disease - Category: Neurology Authors: Source Type: research