Fluorescence-activated cell sorting to reveal the cell origin of radioligand binding

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Date
2019-06-19
Journal Title
Journal ISSN
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Publisher
SAGE
Abstract
Many studies have explored the role of TSPO (18 kDa translocator protein) as a marker of neuroinflammation using single-photon emission computed tomography (SPECT) or positron emission tomography (PET). In vivo imaging does not allow to determine the cells in which TSPO is altered. We propose a methodology based on fluorescence-activated cell sorting to sort different cell types of radioligand-treated tissues. We compared left/right hippocampus of rats in response to a unilateral injection of lipopolysaccharide (LPS), ciliary neurotrophic factor (CNTF) or saline. We finally applied this methodology in human samples (Alzheimer's disease patients and controls). Our data show that the pattern of TSPO overexpression differs across animal models of acute neuroinflammation. LPS induces a microglial expansion and an increase in microglial TSPO binding. CNTF is associated with an increase in TSPO binding in microglia and astrocytes in association with an increase in the number of microglial binding sites per cell. In humans, we show that the increase in CLINDE binding in Alzheimer's disease concerns microglia and astrocytes in the presence of a microglial expansion. Thus, the cellular basis of TSPO overexpression is condition dependent, and alterations in TSPO binding found in PET/SPECT imaging studies cannot be attributed to particular cell types indiscriminately. © 2021 International Society for Cerebral Blood Flow and Metabolism
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Keywords
Nervous system diseases, Fluorescence, Inflammation, Positron computed tomography, Single photon emission computed tomography, Proteins, Ligands
Citation
Tournier, B. B., Tsartsalis, S., Ceyzériat, K., Medina, Z., Fraser, B. H., Grégoire, M. C., Kövari, E. & Millet, P. (2020). Fluorescence-activated cell sorting to reveal the cell origin of radioligand binding. Journal of Cerebral Blood Flow & Metabolism, 40(6), 1242-1255. doi:10.1177/0271678X19860408
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