Neuronal activity increases translocator protein (TSPO) levels
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The mitochondrial protein, translocator protein (TSPO), is a widely used biomarker of neuroinflammation, but its non-selective cellular expression pattern implies roles beyond inflammatory processes. In the present study, we investigated whether neuronal activity modifies TSPO levels in the adult central nervous system. First, we used single-cell RNA sequencing to generate a cellular landscape of basal TSPO gene expression in the hippocampus of adult (12 weeks old) C57BL6/N mice, followed by confocal laser scanning microscopy to verify TSPO protein in neuronal and non-neuronal cell populations. We then quantified TSPO mRNA and protein levels after stimulating neuronal activity with distinct stimuli, including designer receptors exclusively activated by designer drugs (DREADDs), exposure to a novel environment and acute treatment with the psychostimulant drug, amphetamine. Single-cell RNA sequencing demonstrated a non-selective and multi-cellular gene expression pattern of TSPO at basal conditions in the adult mouse hippocampus. Confocal laser scanning microscopy confirmed that TSPO protein is present in neuronal and non-neuronal (astrocytes, microglia, vascular endothelial cells) cells of cortical (medial prefrontal cortex) and subcortical (hippocampus) brain regions. Stimulating neuronal activity through chemogenetic (DREADDs), physiological (novel environment exposure) or psychopharmacological (amphetamine treatment) approaches led to consistent increases in TSPO gene and protein levels in neurons, but not in microglia or astrocytes. Taken together, our findings show that neuronal activity has the potential to modify TSPO levels in the adult central nervous system. These findings challenge the general assumption that altered TSPO expression or binding unequivocally mirrors ongoing neuroinflammation and emphasize the need to consider non-inflammatory interpretations in some physiological or pathological contexts.
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TSPO is expressed in neurons.
“Given that more recent evidence confirms TSPO expression in neurons [44]”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [44]
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Self-citationMitochondrial Translocator Protein (TSPO) Expression in the Brain After Whole Body Gamma Irradiation
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“Given that more recent evidence confirms TSPO expression in neurons [44], along with the established presence in the glial and endothelial cells [26, 45], we were keen to examine the contribution of neurons, glia and endothelial cells to TSPO signal in ME7 mice.”
BackgroundExploring [11C]CPPC as a CSF1R-targeted PET imaging marker for early Parkinson’s disease severity
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In vivo translocator protein in females with autism spectrum disorder: a pilot study
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Microglial Positron Emission Tomography Imaging In Vivo
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Regulation of astrocyte metabolism by mitochondrial translocator protein <scp>18 kDa</scp>
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Parametric Mapping for TSPO PET Imaging with Spectral Analysis Impulsive Response Function
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Neuroglia in hepatic encephalopathy
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Neurodevelopmental and Neuropsychiatric Disorders
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Microglial physiology and function
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Translocator protein and neurodegeneration: insights from Alzheimer’s disease
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- Authors
- Notter, T., Schalbetter, S. M., Clifton, N. E., Mattei, D., Richetto, J., Thomas, K., Meyer, U., & Hall, J.
- Affiliations
- Cardiff University (GB)
- University of Zurich (CH)
- Corresponding author
- Notter, Tina
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2020-05-12
- Volume
- 26
- Issue
- 6
- Pages
- 2025-2037
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC8440208
- OpenAlex
- W3016299128
- Cited by
- 118
- References
- 65
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 24 · 2023: 20 · 2022: 20 · 2021: 24 · 2020: 8
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PZ00P3_18009/1, 188524, 174868, 310030)
- Universität Zürich
- Medical Research Council (MR/L010305/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- translocator protein (TSPO), neuronal activity, neuroinflammation biomarkers, hippocampus, medial prefrontal cortex, amphetamine, astrocytes, microglia, vascular endothelial cells, single-cell RNA sequencing
- MeSH terms
- Animals, Neurons, Microglia, Receptors, GABA, Endothelial Cells, Positron-Emission Tomography, Mice
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