In vivo imaging of astrocytes in the whole brain with engineered AAVs and diffusion-weighted magnetic resonance imaging
Open accessAbstract
Astrocytes constitute a major part of the central nervous system and the delineation of their activity patterns is conducive to a better understanding of brain network dynamics. This study aimed to develop a magnetic resonance imaging (MRI)-based method in order to monitor the brain-wide or region-specific astrocytes in live animals. Adeno-associated virus (AAVs) vectors carrying the human glial fibrillary acidic protein (GFAP) promoter driving the EGFP-AQP1 (Aquaporin-1, an MRI reporter) fusion gene were employed. The following steps were included: constructing recombinant AAV vectors for astrocyte-specific expression, detecting MRI reporters in cell culture, brain regions, or whole brain following cell transduction, stereotactic injection, or tail vein injection. The astrocytes were detected by both fluorescent imaging and Diffusion-weighted MRI. The novel AAV mutation (Site-directed mutagenesis of surface-exposed tyrosine (Y) residues on the AAV5 capsid) significantly increased fluorescence intensity (p < 0.01) compared with the AAV5 wild type. Transduction of the rAAV2/5 carrying AQP1 induced the titer-dependent changes in MRI contrast in cell cultures (p < 0.05) and caudate-putamen (CPu) in the brain (p < 0.05). Furthermore, the MRI revealed a good brain-wide alignment between AQP1 levels and ADC signals, which increased over time in most of the transduced brain regions. In addition, the rAAV2/PHP.eB serotype efficiently introduced AOP1 expression in the whole brain via tail vein injection. This study provides an MRI-based approach to detect dynamic changes in astrocytes in live animals. The novel in vivo tool could help us to understand the complexity of neuronal and glial networks in different pathophysiological conditions.
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The diffusion model appears not only to be able to distinguish between microglia and astrocytes but also to assess the presence of neurodegeneration.
“Interestingly, the model appears not only to be able to distinguish between microglia and astrocytes but also to assess the presence of neurodegeneration [510].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [510]
The Perspective (page unavailable) says the diffusion-weighted MRI method images astrocytes and may identify regions with abnormal astrocytes under pathological conditions. The Assessment of astrocyte-specific rAAV-AQP1 section (page unavailable) mentions microglia only as a marker used to check cytotoxicity; it does not show that the imaging method distinguishes microglia from astrocytes. The paper also does not show that the method assesses the presence of neurodegeneration. (LLM, conf=0.84)
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- Authors
- Li, M., Liu, Z., Wu, Y., Zheng, N., Liu, X., Cai, A., Zheng, D., Zhu, J., Wu, J., Xu, L., Li, X., Zhu, L.-Q., Manyande, A., Xu, F., & Wang, J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Wuhan Institute of Physics and Mathematics (CN)
- Chinese University of Hong Kong (HK)
- Wuhan University (CN)
- Fujian University of Traditional Chinese Medicine (CN)
- Huazhong University of Science and Technology (CN)
- University of West London (GB)
- Corresponding author
- Xu, Fuqiang
- Wang, Jie
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2022-04-28
- Volume
- 29
- Issue
- 3
- Pages
- 545-552
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W4225016307
- Cited by
- 26
- References
- 34
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 3
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- green
- orcid.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- UWL Repository (University of West London) (acceptedVersion)
- Funders
- National Natural Science Foundation of China (31970973, 81974170, 31830035)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- astrocytes, diffusion-weighted imaging, adeno-associated virus vectors, aquaporin-1, AAV5, glial fibrillary acidic protein promoter, in vivo imaging, tail vein injection, stereotactic injection, apparent diffusion coefficient, caudate-putamen
- MeSH terms
- Dependovirus, Animals, Astrocytes, Brain, Cells, Cultured, Genetic Vectors, Glial Fibrillary Acidic Protein, Humans, Male, Promoter Regions, Genetic, Transduction, Genetic, Diffusion Magnetic Resonance Imaging, Green Fluorescent Proteins, Rats, Aquaporin 1
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