Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP‑PS1 mice and human post‑mortem brain samples

Simple item page
dc.contributor.authorSt-Pierre, Marie-Kim
dc.contributor.authorCarrier, Micaël
dc.contributor.authorGonzález Ibáñez, Fernando
dc.contributor.authorKhakpour, Mohammadparsa
dc.contributor.authorWallman, Marie‑Josée
dc.contributor.authorParent, Martin
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-01-25T21:49:26Z
dc.date.available2024-01-25T21:49:26Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.descriptionWe would like to thank Dr. Nathalie Vernoux and Mr. Hassan El Hajj for the perfusion of the mice. We are also thankful to Dr. Luc Vallières for generously providing the APP-PS1 mice used in the study. We acknowledge with respect the Lekwungen peoples on whose traditional territory the University of Victoria stands, and the Songhees, Esquimalt and WSÁNEĆ peoples whose historical relationships with the land continue to this day.en_US
dc.description.abstractThe past decade has witnessed increasing evidence for a crucial role played by glial cells, notably astrocytes, in Alzheimer’s disease (AD). To provide novel insights into the roles of astrocytes in the pathophysiology of AD, we performed a quantitative ultrastructural characterization of their intracellular contents and parenchymal interactions in an aged mouse model of AD pathology, as aging is considered the main risk factor for developing AD. We compared 20-month-old APP-PS1 and age-matched C57BL/6J male mice, among the ventral hippocampus CA1 strata lacunosum-moleculare and radiatum, two hippocampal layers severely affected by AD pathology. Astrocytes in both layers interacted more with synaptic elements and displayed more ultrastructural markers of increased phagolysosomal activity in APP-PS1 versus C57BL6/J mice. In addition, we investigated the ultrastructural heterogeneity of astrocytes, describing in the two examined layers a dark astrocytic state that we characterized in terms of distribution, interactions with AD hallmarks, and intracellular contents. This electron-dense astrocytic state, termed dark astrocytes, was observed throughout the hippocampal parenchyma, closely associated with the vasculature, and possessed several ultrastructural markers of cellular stress. A case study exploring the hippocampal head of an aged human postmortem brain sample also revealed the presence of a similar electron-dense, dark astrocytic state. Overall, our study provides the first ultrastructural quantitative analysis of astrocytes among the hippocampus in aged AD pathology, as well as a thorough characterization of a dark astrocytic state conserved from mouse to human.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipMKSP is supported by doctoral training awards from the Canadian Institutes of Health Research (CIHR) and Fonds de recherche du Québec—Santé (FRQS). MC holds a FRQS doctoral’s training award. FGI was supported by a doctoral scholarship from the Mexican Council of Science and Technology (CONACYT). MET holds a Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition. This work was funded by a CIHR Foundation grant (FDN341846) awarded to MET.en_US
dc.identifier.citationSt-Pierre, M-K., Carrier, M., González Ibáñez, F., Khakpour, M., Wallman, M-J., Parent, M., & Tremblay, M-È. (2023). Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP‑PS1 mice and human post‑mortem brain samples. Journal of Neuroinflammation, 20(73). https://doi.org/10.1186/s12974-023-02752-7en_US
dc.identifier.urihttps://doi.org/10.1186/s12974-023-02752-7
dc.identifier.urihttp://hdl.handle.net/1828/15881
dc.language.isoenen_US
dc.publisherJournal of Neuroinflammationen_US
dc.subjectAstrocytesen_US
dc.subjectHeterogeneityen_US
dc.subjectDark astrocytesen_US
dc.subjectUltrastructureen_US
dc.subjectAgingen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectAPP-PS1 miceen_US
dc.subjectHuman post-mortem brain samplesen_US
dc.titleAstrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP‑PS1 mice and human post‑mortem brain samplesen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
st-pierre_marie-kim_JNeuroinflammation_2023.pdf
Size:
12.7 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Faculty Publications (Medical Sciences)
 
University of Victoria Libraries

We acknowledge and respect the Lək̓ʷəŋən (Songhees and Esquimalt) Peoples on whose territory the university stands, and the Lək̓ʷəŋən and W̱SÁNEĆ Peoples whose historical relationships with the land continue to this day.