Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain

Abstract

Aims: Microglia are involved in neurodegeneration, are prime targets for anti‐inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti‐TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO‐positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti‐inflammatory pharmacological target.

Determination of [11C]PBR28 Binding Potential in vivo: A First Human TSPO Blocking Study

“…1 Therefore, TSPO has become a target for positron emission tomography (PET) radioligands used to quantify the activation and density of these cells in vivo.…”

Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers11C-(R)-PK11195 and18F-GE-180

“…This fact has previously been used to validate TSPO tracers in healthy animals (10). Previously, it has been reported that the TSPO protein is also expressed in the ependymal cells (34) and cells within the choroid plexus (9,35). Additionally, the binding in the olfactory bulbs in rodents has previously been observed (36).…”

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

“…38 Briefly, sections were treated with Target Retrieval Solution (Dako, Carpinteria, CA) for antigen retrieval and then with rabbit anti-HO-1 antibody (Stressgen) at 1:200 for 2 hours at room temperature. ImmPRESS anti-rabbit Ig peroxidase kit (Vector Laboratories Ltd., Burlingame, CA) in combination with diaminobenzidine was used to develop a brown reaction product.…”