| Autor: |
Erik Nutma, Nurun Fancy, Maria Weinert, Manuel C. Marzin, Stergios Tsartsalis, Robert C.J. Muirhead, Irene Falk, Joy de Bruin, David Hollaus, Robin Pieterman, Jasper Anink, David Story, Siddharthan Chandran, Jiabin Tang, Maria C. Trolese, Takashi Saito, Takaomi C. Saido, Katie Wiltshire, Paula Beltran-Lobo, Alexandra Philips, Jack Antel, Luke Healy, Craig S. Moore, Caterina Bendotti, Eleonora Aronica, Carola I. Radulescu, Samuel J. Barnes, David W. Hampton, Paul van der Valk, Steven Jacobson, Paul M. Matthews, Sandra Amor, David R. Owen |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.11.491453 |
| Popis: |
Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells is unique to a subset of species within the Muroidea superfamily of rodents. We show that TSPO is mechanistically linked to classical pro-inflammatory myeloid cell function in rodents but not humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO PET reflects density of inflammatory cells rather than activation state. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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