Contributions
Abstract: EP1454
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
The 18 kDa translocator protein is a mitochondrial transmembrane protein that is lowly expressed in the healthy CNS but strongly upregulated in CNS injury and thus of interest as a biomarker of neuroinflammation. TSPO is abundantly expressed in activated microglia and macrophages, and numerous studies have shown the transporter to be highly upregulated in inflammatory CNS lesions in multiple sclerosis (MS) and animal models of experimental autoimmune encephalomyelitis (EAE). Marmosets are small New World monkeys of particular interest for their neurological similarity to humans, which renders them a powerful model of neuroinflammatory disease. Most crucially, marmosets exhibit white matter-grey matter ratios similar to those of humans, and EAE marmosets manifest lesions that are pathologically and radiologically similar to lesions seen in MS patients. However, TSPO expression in marmoset EAE remains largely uncharacterized.
To better understand the utility of TSPO as a biomarker of inflammation in EAE, this study seeks to characterize the cellular localization of TSPO in marmoset EAE by immunohistochemical analysis of pathological brain and spinal cord tissues. Specifically, this study characterizes the cellular localization of TSPO and the immunophenotype of TSPO+ microglia/macrophages at different stages of lesion development. Our study confirms the common marmoset model of EAE to recapitulate the expression of TSPO in microglia and macrophages that is observed in rodent models. In early lesions that are less than 4 weeks old (as determined by serial magnetic resonance imaging scans), TSPO is expressed in over 90% of Iba1+ microglia/macrophages, particularly in the hypercellular nodules observed at the core of many lesions. In these Iba1+TSPO+ cells, TSPO is frequently co-expressed with MRP14, a marker of early activation, and CD74, the invariant chain of HLA-DR. In older lesions (over 7 months old), TSPO expression is observed in less than 15% of Iba1+ cells, and the percentage of Iba1+TSPO+ cells co-expressing MRP14 or HLA-DR is also observed to decrease. These findings gives insight into the timecourse of TSPO expression in neuroinflammation, which has significant implications for its clinical utility as an imaging target in the monitoring of neuroinflammatory disease.
Disclosure: Irene Falk: Nothing to disclose.
Abstract: EP1454
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
The 18 kDa translocator protein is a mitochondrial transmembrane protein that is lowly expressed in the healthy CNS but strongly upregulated in CNS injury and thus of interest as a biomarker of neuroinflammation. TSPO is abundantly expressed in activated microglia and macrophages, and numerous studies have shown the transporter to be highly upregulated in inflammatory CNS lesions in multiple sclerosis (MS) and animal models of experimental autoimmune encephalomyelitis (EAE). Marmosets are small New World monkeys of particular interest for their neurological similarity to humans, which renders them a powerful model of neuroinflammatory disease. Most crucially, marmosets exhibit white matter-grey matter ratios similar to those of humans, and EAE marmosets manifest lesions that are pathologically and radiologically similar to lesions seen in MS patients. However, TSPO expression in marmoset EAE remains largely uncharacterized.
To better understand the utility of TSPO as a biomarker of inflammation in EAE, this study seeks to characterize the cellular localization of TSPO in marmoset EAE by immunohistochemical analysis of pathological brain and spinal cord tissues. Specifically, this study characterizes the cellular localization of TSPO and the immunophenotype of TSPO+ microglia/macrophages at different stages of lesion development. Our study confirms the common marmoset model of EAE to recapitulate the expression of TSPO in microglia and macrophages that is observed in rodent models. In early lesions that are less than 4 weeks old (as determined by serial magnetic resonance imaging scans), TSPO is expressed in over 90% of Iba1+ microglia/macrophages, particularly in the hypercellular nodules observed at the core of many lesions. In these Iba1+TSPO+ cells, TSPO is frequently co-expressed with MRP14, a marker of early activation, and CD74, the invariant chain of HLA-DR. In older lesions (over 7 months old), TSPO expression is observed in less than 15% of Iba1+ cells, and the percentage of Iba1+TSPO+ cells co-expressing MRP14 or HLA-DR is also observed to decrease. These findings gives insight into the timecourse of TSPO expression in neuroinflammation, which has significant implications for its clinical utility as an imaging target in the monitoring of neuroinflammatory disease.
Disclosure: Irene Falk: Nothing to disclose.