Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Related Experiment Video

Updated: Jun 17, 2026

In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
12:48

In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Published on: May 11, 2015

10.6K

Erik Nutma1,2, Nurun Fancy3,4, Maria Weinert3

  • 1Department of Pathology, Amsterdam UMC - Location VUmc, Amsterdam, The Netherlands.

Nature Communications
|August 28, 2023
PubMed

Insights

Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) shows inflammation in brain disease models. However, TSPO PET signals in humans reflect inflammatory cell density, not their activation state, due to species-specific gene regulation.

Area of Science:

  • Neuroscience
  • Immunology
  • Medical Imaging

Background:

  • Microglial activation is key in neuroinflammation and neurodegeneration.
  • 18 kDa Translocator Protein (TSPO) positron emission tomography (PET) is used to detect in vivo inflammation.
  • Quantitative interpretation of TSPO-PET imaging is challenging.

Purpose of the Study:

  • To investigate species-specific differences in TSPO expression during microglial activation.
  • To clarify the utility of TSPO-PET for assessing neuroinflammation in humans.
  • To identify novel biomarkers for human microglial activation.

Main Methods:

  • Comparative analysis of TSPO expression in mouse, non-human primate, and human disease models.
  • Genetic analysis of the TSPO gene promoter region.
  • Identification of potential microglial activation markers using transcriptomic data.

Main Results:

  • TSPO expression increases in activated microglia in mouse models but not in non-human primates or humans with neurodegenerative/neuroinflammatory diseases.
  • Genetic divergence in the TSPO promoter explains species-specific regulation of TSPO expression, linked to AP1 transcription factor activity in rodents.
  • LCP2 and TFEC are proposed as potential human microglial activation markers.

Conclusions:

  • TSPO expression in human myeloid cells differs from that in rodents.
  • TSPO-PET imaging in humans indicates inflammatory cell density rather than their activation state.
  • Novel biomarkers like LCP2 and TFEC may offer better insights into human microglial activation.

More Related Videos

Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain10:40

Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain

Published on: October 27, 2019

32.3K
Fluorescence-Activated Cell Sorting-Radioligand Treated Tissue FACS-RTT to Determine the Cellular Origin of Radioactive Signal12:04

Fluorescence-Activated Cell Sorting-Radioligand Treated Tissue FACS-RTT to Determine the Cellular Origin of Radioactive Signal

Published on: September 10, 2021

2.4K

Related Concept Videos

The Central Dogma01:25

The Central Dogma

Overview
Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
Forced Transdifferentiation01:28

Forced Transdifferentiation

Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...