Characteristics of TSPO expression in marmoset EAE
Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target th...
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03343-4 |
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| author | Irene Falk Dragan Maric Emily Leibovitch Pascal Sati Jennifer Lefeuvre Nicholas J. Luciano Joseph Guy Seung-Kwon Ha David R. Owen Franklin Aigbirhio Paul M. Matthews Daniel S. Reich Steven Jacobson |
| author_facet | Irene Falk Dragan Maric Emily Leibovitch Pascal Sati Jennifer Lefeuvre Nicholas J. Luciano Joseph Guy Seung-Kwon Ha David R. Owen Franklin Aigbirhio Paul M. Matthews Daniel S. Reich Steven Jacobson |
| author_sort | Irene Falk |
| collection | DOAJ |
| description | Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target. However, its specific pathological significance in humans is not well understood. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a well-established primate model of MS. Studying TSPO expression in this model will enhance our understanding of its expression in MS. This study therefore characterizes patterns of TSPO expression in fixed CNS tissues from one non-EAE control marmoset and 8 EAE marmosets using multiplex immunofluorescence. In control CNS tissue, we find that TSPO is expressed in the leptomeninges, ependyma, and over two-thirds of Iba1 + microglia, but not astrocytes or neurons. In Iba1 + cells in both control and acute EAE tissue, we find that TSPO is co-expressed with markers of antigen presentation (CD74), early activation (MRP14), phagocytosis (CD163) and anti-inflammatory phenotype (Arg1); a high level of TSPO expression is not restricted to a particular microglial phenotype. While TSPO is expressed in over 88% of activated Iba1 + cells in acute lesions in marmoset EAE, it also is sometimes observed in subsets of astrocytes and neurons. Additionally, we find the percentage of Iba1 + cells expressing TSPO declines significantly in lesions > 5 months old and may be as low as 13% in chronic lesions. However, we also find increased astrocytic TSPO expression in chronic-appearing lesions with astrogliosis. Finally, we find expression of TSPO in a subset of neurons, most frequently GLS2 + glutamatergic neurons. The shift in TSPO expression from Iba + microglia/macrophages to astrocytes over time is similar to patterns suggested by earlier neuropathology studies in MS. Thus, marmoset EAE appears to be a clinically relevant model for the study of TSPO in immune dysregulation in human disease. Graphical Abstract |
| format | Article |
| id | doaj-art-663b77ed6d2f4bbf99a82dbdfda42d56 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj-art-663b77ed6d2f4bbf99a82dbdfda42d562025-02-02T12:35:02ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111610.1186/s12974-025-03343-4Characteristics of TSPO expression in marmoset EAEIrene Falk0Dragan Maric1Emily Leibovitch2Pascal Sati3Jennifer Lefeuvre4Nicholas J. Luciano5Joseph Guy6Seung-Kwon Ha7David R. Owen8Franklin Aigbirhio9Paul M. Matthews10Daniel S. Reich11Steven Jacobson12Viral Immunology Section, National Institute of Neurological Diseases and Stroke, National Institutes of HealthFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of HealthViral Immunology Section, National Institute of Neurological Diseases and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthDepartment of Brain Sciences, Imperial College LondonMolecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, University of CambridgeDepartment of Brain Sciences, Imperial College LondonTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthViral Immunology Section, National Institute of Neurological Diseases and Stroke, National Institutes of HealthAbstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target. However, its specific pathological significance in humans is not well understood. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a well-established primate model of MS. Studying TSPO expression in this model will enhance our understanding of its expression in MS. This study therefore characterizes patterns of TSPO expression in fixed CNS tissues from one non-EAE control marmoset and 8 EAE marmosets using multiplex immunofluorescence. In control CNS tissue, we find that TSPO is expressed in the leptomeninges, ependyma, and over two-thirds of Iba1 + microglia, but not astrocytes or neurons. In Iba1 + cells in both control and acute EAE tissue, we find that TSPO is co-expressed with markers of antigen presentation (CD74), early activation (MRP14), phagocytosis (CD163) and anti-inflammatory phenotype (Arg1); a high level of TSPO expression is not restricted to a particular microglial phenotype. While TSPO is expressed in over 88% of activated Iba1 + cells in acute lesions in marmoset EAE, it also is sometimes observed in subsets of astrocytes and neurons. Additionally, we find the percentage of Iba1 + cells expressing TSPO declines significantly in lesions > 5 months old and may be as low as 13% in chronic lesions. However, we also find increased astrocytic TSPO expression in chronic-appearing lesions with astrogliosis. Finally, we find expression of TSPO in a subset of neurons, most frequently GLS2 + glutamatergic neurons. The shift in TSPO expression from Iba + microglia/macrophages to astrocytes over time is similar to patterns suggested by earlier neuropathology studies in MS. Thus, marmoset EAE appears to be a clinically relevant model for the study of TSPO in immune dysregulation in human disease. Graphical Abstracthttps://doi.org/10.1186/s12974-025-03343-4TSPOPET imagingMultiple sclerosisExperimental autoimmune encephalomyelitis |
| spellingShingle | Irene Falk Dragan Maric Emily Leibovitch Pascal Sati Jennifer Lefeuvre Nicholas J. Luciano Joseph Guy Seung-Kwon Ha David R. Owen Franklin Aigbirhio Paul M. Matthews Daniel S. Reich Steven Jacobson Characteristics of TSPO expression in marmoset EAE Journal of Neuroinflammation TSPO PET imaging Multiple sclerosis Experimental autoimmune encephalomyelitis |
| title | Characteristics of TSPO expression in marmoset EAE |
| title_full | Characteristics of TSPO expression in marmoset EAE |
| title_fullStr | Characteristics of TSPO expression in marmoset EAE |
| title_full_unstemmed | Characteristics of TSPO expression in marmoset EAE |
| title_short | Characteristics of TSPO expression in marmoset EAE |
| title_sort | characteristics of tspo expression in marmoset eae |
| topic | TSPO PET imaging Multiple sclerosis Experimental autoimmune encephalomyelitis |
| url | https://doi.org/10.1186/s12974-025-03343-4 |
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