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Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes

Velasco-Estevez, María; Mampay, Myrthe; Boutin, Hervé; Chaney, Aisling; Warn, Peter; Sharp, Andrew; Burgess, Ellie; Moeendarbary, Emad; Dev, Kumlesh K.; Sheridan, Graham K.

Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes Thumbnail


Authors

María Velasco-Estevez

Myrthe Mampay

Hervé Boutin

Aisling Chaney

Peter Warn

Andrew Sharp

Ellie Burgess

Emad Moeendarbary

Kumlesh K. Dev



Contributors

Abstract

© 2018 Velasco-Estevez, Mampay, Boutin, Chaney, Warn, Sharp, Burgess, Moeendarbary, Dev and Sheridan. A defining pathophysiological hallmark of Alzheimer's disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Aβ142 peptides. Amyloid plaques are hard, brittle structures scattered throughout the hippocampus and cerebral cortex and are thought to cause hyperphosphorylation of tau, neurofibrillary tangles, and progressive neurodegeneration. Reactive astrocytes and microglia envelop the exterior of amyloid plaques and infiltrate their inner core. Glia are highly mechanosensitive cells and can almost certainly sense the mismatch between the normally soft mechanical environment of the brain and very stiff amyloid plaques via mechanosensing ion channels. Piezo1, a non-selective cation channel, can translate extracellular mechanical forces to intracellular molecular signaling cascades through a process known as mechanotransduction. Here, we utilized an aging transgenic rat model of AD (TgF344-AD) to study expression of mechanosensing Piezo1 ion channels in amyloid plaque-reactive astrocytes. We found that Piezo1 is upregulated with age in the hippocampus and cortex of 18-month old wild-type rats. However, more striking increases in Piezo1 were measured in the hippocampus of TgF344-AD rats compared to age-matched wild-type controls. Interestingly, repeated urinary tract infections with Escherichia coli bacteria, a common comorbidity in elderly people with dementia, caused further elevations in Piezo1 channel expression in the hippocampus and cortex of TgF344-AD rats. Taken together, we report that aging and peripheral infection augment amyloid plaque-induced upregulation of mechanoresponsive ion channels, such as Piezo1, in astrocytes. Further research is required to investigate the role of astrocytic Piezo1 in the Alzheimer's brain, whether modulating channel opening will protect or exacerbate the disease state, and most importantly, if Piezo1 could prove to be a novel drug target for age-related dementia.

Citation

Velasco-Estevez, M., Mampay, M., Boutin, H., Chaney, A., Warn, P., Sharp, A., …Sheridan, G. K. (2018). Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes. Frontiers in Aging Neuroscience, 10, Article 332. https://doi.org/10.3389/fnagi.2018.00332

Journal Article Type Article
Acceptance Date Oct 1, 2018
Online Publication Date Oct 22, 2018
Publication Date Oct 22, 2018
Deposit Date Jan 13, 2020
Publicly Available Date Jan 15, 2020
Journal Frontiers in Aging Neuroscience
Electronic ISSN 1663-4365
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 10
Article Number 332
DOI https://doi.org/10.3389/fnagi.2018.00332
Public URL https://nottingham-repository.worktribe.com/output/2918123
Publisher URL https://www.frontiersin.org/articles/10.3389/fnagi.2018.00332/full

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