Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound
Abstract Transcranial scanning ultrasound combined with intravenously injected microbubbles (SUS+MB) has been shown to transiently open the blood–brain barrier and reduce the amyloid‐β (Aβ) pathology in the APP23 mouse model of Alzheimer's disease (AD). This has been accomplished through the ac...
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| Format: | Article |
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Wiley
2023-01-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10329 |
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| author | Gerhard Leinenga Liviu‐Gabriel Bodea Jan Schröder Giuzhi Sun Yichen Zhou Jae Song Alexandra Grubman Jose M. Polo Jürgen Götz |
| author_facet | Gerhard Leinenga Liviu‐Gabriel Bodea Jan Schröder Giuzhi Sun Yichen Zhou Jae Song Alexandra Grubman Jose M. Polo Jürgen Götz |
| author_sort | Gerhard Leinenga |
| collection | DOAJ |
| description | Abstract Transcranial scanning ultrasound combined with intravenously injected microbubbles (SUS+MB) has been shown to transiently open the blood–brain barrier and reduce the amyloid‐β (Aβ) pathology in the APP23 mouse model of Alzheimer's disease (AD). This has been accomplished through the activation of microglial cells; however, their response to the SUS treatment is incompletely understood. Here, wild‐type (WT) and APP23 mice were subjected to SUS+MB, using nonsonicated mice as sham controls. After 48 h, the APP23 mice were injected with methoxy‐XO4 to label Aβ aggregates, followed by microglial isolation into XO4+ and XO4− populations using flow cytometry. Both XO4+ and XO4− cells were subjected to RNA sequencing and transcriptome profiling. The analysis of the microglial cells revealed a clear segregation depending on genotype (AD model vs. WT mice) and Aβ internalization (XO4+ vs. XO4− microglia), but interestingly, no differences were found between SUS+MB and sham in WT mice. Differential gene expression analysis in APP23 mice detected 278 genes that were significantly changed by SUS+MB in the XO4+ cells (248 up/30 down) and 242 in XO− cells (225 up/17 down). Pathway analysis highlighted differential expression of genes related to the phagosome pathway and marked upregulation of cell cycle‐related transcripts in XO4+ and XO4‐ microglia isolated from SUS+MB‐treated APP23 mice. Together, this highlights the complexity of the microglial response to transcranial ultrasound, with potential applications for the treatment of AD. |
| format | Article |
| id | doaj-art-4eada074200a42d6b53a82eee438c48a |
| institution | Kabale University |
| issn | 2380-6761 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-4eada074200a42d6b53a82eee438c48a2024-11-21T05:16:02ZengWileyBioengineering & Translational Medicine2380-67612023-01-0181n/an/a10.1002/btm2.10329Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasoundGerhard Leinenga0Liviu‐Gabriel Bodea1Jan Schröder2Giuzhi Sun3Yichen Zhou4Jae Song5Alexandra Grubman6Jose M. Polo7Jürgen Götz8Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland Brisbane (St Lucia Campus) Queensland AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland Brisbane (St Lucia Campus) Queensland AustraliaDepartment of Anatomy & Developmental Biology and the Australian Regenerative Medicine Institute Monash University Melbourne Victoria AustraliaDepartment of Anatomy & Developmental Biology and the Australian Regenerative Medicine Institute Monash University Melbourne Victoria AustraliaDepartment of Anatomy & Developmental Biology and the Australian Regenerative Medicine Institute Monash University Melbourne Victoria AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland Brisbane (St Lucia Campus) Queensland AustraliaDepartment of Anatomy & Developmental Biology and the Australian Regenerative Medicine Institute Monash University Melbourne Victoria AustraliaDepartment of Anatomy & Developmental Biology and the Australian Regenerative Medicine Institute Monash University Melbourne Victoria AustraliaClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland Brisbane (St Lucia Campus) Queensland AustraliaAbstract Transcranial scanning ultrasound combined with intravenously injected microbubbles (SUS+MB) has been shown to transiently open the blood–brain barrier and reduce the amyloid‐β (Aβ) pathology in the APP23 mouse model of Alzheimer's disease (AD). This has been accomplished through the activation of microglial cells; however, their response to the SUS treatment is incompletely understood. Here, wild‐type (WT) and APP23 mice were subjected to SUS+MB, using nonsonicated mice as sham controls. After 48 h, the APP23 mice were injected with methoxy‐XO4 to label Aβ aggregates, followed by microglial isolation into XO4+ and XO4− populations using flow cytometry. Both XO4+ and XO4− cells were subjected to RNA sequencing and transcriptome profiling. The analysis of the microglial cells revealed a clear segregation depending on genotype (AD model vs. WT mice) and Aβ internalization (XO4+ vs. XO4− microglia), but interestingly, no differences were found between SUS+MB and sham in WT mice. Differential gene expression analysis in APP23 mice detected 278 genes that were significantly changed by SUS+MB in the XO4+ cells (248 up/30 down) and 242 in XO− cells (225 up/17 down). Pathway analysis highlighted differential expression of genes related to the phagosome pathway and marked upregulation of cell cycle‐related transcripts in XO4+ and XO4‐ microglia isolated from SUS+MB‐treated APP23 mice. Together, this highlights the complexity of the microglial response to transcranial ultrasound, with potential applications for the treatment of AD.https://doi.org/10.1002/btm2.10329Alzheimer's diseasemethoxy‐XO4microgliaRNA sequencingtranscriptomicsultrasound |
| spellingShingle | Gerhard Leinenga Liviu‐Gabriel Bodea Jan Schröder Giuzhi Sun Yichen Zhou Jae Song Alexandra Grubman Jose M. Polo Jürgen Götz Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound Bioengineering & Translational Medicine Alzheimer's disease methoxy‐XO4 microglia RNA sequencing transcriptomics ultrasound |
| title | Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound |
| title_full | Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound |
| title_fullStr | Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound |
| title_full_unstemmed | Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound |
| title_short | Transcriptional signature in microglia isolated from an Alzheimer's disease mouse model treated with scanning ultrasound |
| title_sort | transcriptional signature in microglia isolated from an alzheimer s disease mouse model treated with scanning ultrasound |
| topic | Alzheimer's disease methoxy‐XO4 microglia RNA sequencing transcriptomics ultrasound |
| url | https://doi.org/10.1002/btm2.10329 |
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