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

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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A defining pathophysiological hallmark of Alzheimer’s disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Ab1-42 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.
Original languageEnglish
Article number332
Pages (from-to)1-18
Number of pages18
JournalFrontiers in Aging Neuroscience
Volume10
DOIs
Publication statusPublished - 22 Oct 2018

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Amyloid Plaques
Astrocytes
Alzheimer Disease
Hippocampus
Infection
Ion Channels
Dementia
Transgenic Rats
Neurofibrillary Tangles
Brain
Microglia
Urinary Tract Infections
Neuroglia
Cerebral Cortex
Cations
Comorbidity
Up-Regulation
Escherichia coli
Bacteria
Peptides

Bibliographical note

© 2018 Velasco-Estevez, Mampay, Boutin, Chaney, Warn, Sharp, Burgess, Moeendarbary, Dev and Sheridan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Cite this

Velasco-Estevez, Maria ; Mampay, Myrthe ; Boutin, Herve ; Chaney, Aisling ; Warn, Peter ; Sharp, Andrew ; Burgess, Ellie ; Moeendarbary, Emad ; Dev, Kumlesh K. ; Sheridan, Graham. / Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes. In: Frontiers in Aging Neuroscience. 2018 ; Vol. 10. pp. 1-18.
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abstract = "A defining pathophysiological hallmark of Alzheimer’s disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Ab1-42 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-matchedwild-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.",
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Velasco-Estevez, M, Mampay, M, Boutin, H, Chaney, A, Warn, P, Sharp, A, Burgess, E, Moeendarbary, E, Dev, KK & Sheridan, G 2018, 'Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes' Frontiers in Aging Neuroscience, vol. 10, 332, pp. 1-18. https://doi.org/10.3389/fnagi.2018.00332

Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes. / Velasco-Estevez, Maria; Mampay, Myrthe; Boutin, Herve; Chaney, Aisling; Warn, Peter ; Sharp, Andrew ; Burgess, Ellie; Moeendarbary, Emad; Dev, Kumlesh K.; Sheridan, Graham.

In: Frontiers in Aging Neuroscience, Vol. 10, 332, 22.10.2018, p. 1-18.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Chaney, Aisling

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AU - Dev, Kumlesh K.

AU - Sheridan, Graham

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N2 - A defining pathophysiological hallmark of Alzheimer’s disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Ab1-42 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-matchedwild-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.

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