Hall, Chloe M;
Lasli, Soufian;
Serwinski, Bianca;
Djordjevic, Boris;
Sheridan, Graham K;
Moeendarbary, Emad;
(2023)
Hippocampus of the APPNL-G-F mouse model of Alzheimer’s disease exhibits region-specific tissue softening concomitant with elevated astrogliosis.
Frontiers in Aging Neuroscience
, 15
, Article 1212212. 10.3389/fnagi.2023.1212212.
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Abstract
Widespread neurodegeneration, enlargement of cerebral ventricles, and atrophy of cortical and hippocampal brain structures are classic hallmarks of Alzheimer’s disease (AD). Prominent macroscopic disturbances to the cytoarchitecture of the AD brain occur alongside changes in the mechanical properties of brain tissue, as reported in recent magnetic resonance elastography (MRE) measurements of human brain mechanics. Whilst MRE has many advantages, a significant shortcoming is its spatial resolution. Higher resolution “cellular scale” assessment of the mechanical alterations to brain regions involved in memory formation, such as the hippocampus, could provide fresh new insight into the etiology of AD. Characterization of brain tissue mechanics at the cellular length scale is the first stepping-stone to understanding how mechanosensitive neurons and glia are impacted by neurodegenerative disease-associated changes in their microenvironment. To provide insight into the microscale mechanics of aging brain tissue, we measured spatiotemporal changes in the mechanical properties of the hippocampus using high resolution atomic force microscopy (AFM) indentation tests on acute brain slices from young and aged wild-type mice and the APPNL–G–F mouse model. Several hippocampal regions in APPNL–G–F mice are significantly softer than age-matched wild-types, notably the dentate granule cell layer and the CA1 pyramidal cell layer. Interestingly, regional softening coincides with an increase in astrocyte reactivity, suggesting that amyloid pathology-mediated alterations to the mechanical properties of brain tissue may impact the function of mechanosensitive astrocytes. Our data also raise questions as to whether aberrant mechanotransduction signaling could impact the susceptibility of neurons to cellular stressors in their microenvironment.
| Type: | Article |
|---|---|
| Title: | Hippocampus of the APPNL-G-F mouse model of Alzheimer’s disease exhibits region-specific tissue softening concomitant with elevated astrogliosis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnagi.2023.1212212 |
| Publisher version: | https://doi.org/10.3389/fnagi.2023.1212212 |
| Language: | English |
| Additional information: | © 2023 Hall, Lasli, Serwinski, Djordjevic, Sheridan and Moeendarbary. 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 |
| Keywords: | Alzheimer’s disease, atomic force microscopy, brain tissue elasticity, healthy aging, hippocampus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10175592 |
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