The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.
Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies
Open accessAbstract
We demonstrate the significance of peripheral benzodiazepine receptor (PBR) imaging in living mouse models of Alzheimer's disease (AD) as biomarkers and functional signatures of glial activation. By radiochemically and immunohistochemically analyzing murine models of the two pathological hallmarks of AD, we found that AD-like Aβ deposition is concurrent with astrocyte-dominant PBR expression, in striking contrast with nonastroglial PBR upregulation in accumulations of AD-like phosphorylated tau. Because tau-induced massive neuronal loss was distinct from the marginal neurodegeneration associated with Aβ plaques in these models, cellular localization of PBR reflected deleterious and beneficial glial reactions to tau versus Aβ pathologies, respectively. This notion was subsequently examined in models of various non-AD neuropathologies, revealing the following reactive glial dynamics underlying differential PBR upregulation: (1) PBR(−) astrogliosis uncoupled with microgliosis or coupled with PBR(+) microgliosis associated with irreversible neuronal insults; and (2) PBR(+) astrogliosis coupled with PBR(− or ±) microgliosis associated with minimal or reversible neuronal toxicity. Intracranial transplantation of microglia also indicated that nontoxic microglia drives astroglial PBR expression. Moreover, levels of glial cell line-derived neurotrophic factor (GDNF) in astrocytes were correlated with astroglial PBR, except for increased GDNF in PBR(-) astrocytes in the model of AD-like tau pathology, thereby suggesting that PBR upregulation in astrocytes is an indicator of neurotrophic support. Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD.
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“Similarly, others have found that TSPO positive microglia, astrocytes and endothelium are all increased in models of Alzheimer’s-like neurodegeneration [48–51] and in postmortem human Alzheimer’s disease brains [27].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [48]
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Self-citationTwo amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
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Self-citationDirect brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease
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Loggia, M. L., Chonde, D. B., Akeju, O., Arabasz, G., Catana, C., Edwards, R. R., Hill, E., Hsu, S., Izquierdo-Garcia, D., Ji, R.-R., et al. (2015) · Brain · doi:10.1093/brain/awu377 · Cited by 503
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Metadata
- Authors
- Ji, B., Maeda, J., Sawada, M., Ono, M., Okauchi, T., Inaji, M., Zhang, M.-R., Suzuki, K., Ando, K., Staufenbiel, M., Trojanowski, J. Q., Lee, V. M. Y., Higuchi, M., & Suhara, T.
- Affiliations
- National Institute of Radiological Sciences (JP)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Central Institute for Experimental Animals (JP)
- Novartis (Switzerland) (CH)
- University of Pennsylvania (US)
- Corresponding author
- Higuchi, Makoto
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-11-19
- Volume
- 28
- Issue
- 47
- Pages
- 12255-12267
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2755188
- OpenAlex
- W2030029215
- Cited by
- 169
- References
- 71
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 16 · 2020: 13 · 2019: 4 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 14 · 2014: 12 · 2013: 9 · 2012: 10
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (20023036)
- National Institute on Aging (P30AG010124)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- translocator protein (TSPO), Alzheimer's disease, glial activation, astrocyte activation, microglial activation, amyloid plaques, tau pathology, neurodegeneration, glial cell line-derived neurotrophic factor, neurotrophic support, neuroinflammation, neuroimaging biomarkers, mouse model
- MeSH terms
- Acetamides, Alzheimer Disease, Analysis of Variance, Animals, Cell Line, Transformed, Central Nervous System, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Kainic Acid, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenyl Ethers, Receptors, GABA-A, Amyloid beta-Protein Precursor, Oxidopamine, tau Proteins, Microglia, Cell Transplantation, Radiopharmaceuticals, Neurotoxicity Syndromes, Positron-Emission Tomography, Glial Cell Line-Derived Neurotrophic Factor, Mice, Rats, Plaque, Amyloid
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