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| Status |
Public on May 01, 2022 |
| Title |
Neuronal Activity Increases Translocator Protein (TSPO) Levels in the Adult Mouse Brain |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: 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. The present study investigated whether neuronal activity modifies TSPO expression in the adult central nervous system.
Methods: Single-cell RNA sequencing was performed to generate a cellular landscape of basal TSPO gene expression in the hippocampus of adult (12 weeks old) C57BL6/N mice, whereas confocal laser scanning microscopy was used to verify TSPO protein in neuronal and non-neuronal cell populations. TSPO RNA and protein were quantified 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.
Results: 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 expressed 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.
Conclusions: Neuronal activity has the potential to modify TSPO expression in the adult central nervous system. These findings challenge the general assumption that altered TSPO levels unequivocally mirrors ongoing neuroinflammation and emphasize the need to consider non-inflammatory interpretations in some physiological or pathological contexts.
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| Overall design |
Single-cell RNA sequencing was performed to generate a cellular landscape of basal TSPO gene expression in the hippocampus of adult (12 weeks old) C57BL6/N mice, whereas confocal laser scanning microscopy was used to verify TSPO protein in neuronal and non-neuronal cell populations. TSPO RNA and protein were quantified 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.
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| Contributor(s) |
Notter T, Schalbetter SM, Clifton NE, Mattei D, Richetto J, Meyer U, Hall J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 13, 2020 |
| Last update date |
May 02, 2022 |
| Contact name |
Hubert Rehrauer |
| E-mail(s) |
Hubert.Rehrauer@fgcz.ethz.ch
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| Organization name |
ETH Zurich / University of Zurich
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| Department |
FGCZ
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| Street address |
Winterthurerstr. 190
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| City |
Zurich |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA632602 |
| SRA |
SRP261491 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE150508_RAW.tar |
56.1 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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