Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples
Abstract The 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 t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02752-7 |
| _version_ | 1797864000625573888 |
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| author | Marie-Kim St-Pierre Micaël Carrier Fernando González Ibáñez Mohammadparsa Khakpour Marie-Josée Wallman Martin Parent Marie-Ève Tremblay |
| author_facet | Marie-Kim St-Pierre Micaël Carrier Fernando González Ibáñez Mohammadparsa Khakpour Marie-Josée Wallman Martin Parent Marie-Ève Tremblay |
| author_sort | Marie-Kim St-Pierre |
| collection | DOAJ |
| description | Abstract The 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 post-mortem 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. |
| first_indexed | 2024-04-09T22:44:31Z |
| format | Article |
| id | doaj.art-20307c08ad6b4ccb9ba82d74e2a7f672 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-09T22:44:31Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-20307c08ad6b4ccb9ba82d74e2a7f6722023-03-22T11:55:30ZengBMCJournal of Neuroinflammation1742-20942023-03-0120112710.1186/s12974-023-02752-7Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samplesMarie-Kim St-Pierre0Micaël Carrier1Fernando González Ibáñez2Mohammadparsa Khakpour3Marie-Josée Wallman4Martin Parent5Marie-Ève Tremblay6Axe Neurosciences, Centre de Recherche du CHU de Québec-Université LavalAxe Neurosciences, Centre de Recherche du CHU de Québec-Université LavalAxe Neurosciences, Centre de Recherche du CHU de Québec-Université LavalDivision of Medical Sciences, Medical Sciences Building, University of VictoriaDépartement de Psychiatrie et de Neurosciences, Faculté de Médecine, Université LavalDépartement de Psychiatrie et de Neurosciences, Faculté de Médecine, Université LavalAxe Neurosciences, Centre de Recherche du CHU de Québec-Université LavalAbstract The 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 post-mortem 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.https://doi.org/10.1186/s12974-023-02752-7AstrocytesHeterogeneityDark astrocytesUltrastructureAgingAlzheimer’s disease |
| spellingShingle | Marie-Kim St-Pierre Micaël Carrier Fernando González Ibáñez Mohammadparsa Khakpour Marie-Josée Wallman Martin Parent Marie-Ève Tremblay Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples Journal of Neuroinflammation Astrocytes Heterogeneity Dark astrocytes Ultrastructure Aging Alzheimer’s disease |
| title | Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples |
| title_full | Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples |
| title_fullStr | Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples |
| title_full_unstemmed | Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples |
| title_short | Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples |
| title_sort | astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged app ps1 mice and human post mortem brain samples |
| topic | Astrocytes Heterogeneity Dark astrocytes Ultrastructure Aging Alzheimer’s disease |
| url | https://doi.org/10.1186/s12974-023-02752-7 |
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