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J Cereb Blood Flow Metab. 2019 Jun 26:271678X19860408. doi: 10.1177/0271678X19860408. [Epub ahead of print]

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

Author information

1
1 Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
2
2 Division of Nuclear medicine, University Hospitals of Geneva, Geneva, Switzerland.
3
3 ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Sydney, NSW, Australia.
4
4 Division of Geriatric Psychiatry, Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
5
5 Department of Psychiatry, University of Geneva, Geneva, Switzerland.

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.

KEYWORDS:

Alzheimer's disease; fluorescence-activated cell sorting; neuroinflammation; positron emission tomography/single-photon emission computed tomography; translocator protein

PMID:
31242048
DOI:
10.1177/0271678X19860408

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