Neuronal activity increases translocator protein (TSPO) levels

Notter, Tina, Schalbetter, Sina M., Clifton, Nicholas E. ORCID: https://orcid.org/0000-0003-2597-5253, Mattei, Daniele, Richetto, Juliet, Thomas, Kerrie ORCID: https://orcid.org/0000-0003-3355-9583, Meyer, Urs and Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 2021. Neuronal activity increases translocator protein (TSPO) levels. Molecular Psychiatry 26 , pp. 2025-2037. 10.1038/s41380-020-0745-1

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License.
Publisher:	Springer Nature
ISSN:	1359-4184
Date of First Compliant Deposit:	14 April 2020
Date of Acceptance:	20 April 2020
Last Modified:	08 Jul 2023 17:47
URI:	https://orca.cardiff.ac.uk/id/eprint/130979

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