Dataset Information

Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography.

ABSTRACT: Understanding the mechanisms underlying progression in multiple sclerosis (MS) is one of the key elements contributing to the identification of appropriate therapeutic targets for this under-managed condition. In addition to plaque-related focal inflammatory pathology typical for relapsing remitting MS there are, in progressive MS, widespread diffuse alterations in brain areas outside the focal lesions. This diffuse pathology is tightly related to microglial activation and is co-localized with signs of neurodegeneration. Microglia are brain-resident cells of the innate immune system and overactivation of microglia is associated with several neurodegenerative diseases. Understanding the role of microglial activation in relation to developing neurodegeneration and disease progression may provide a key to developing therapies to target progressive MS. 18-kDa translocator protein (TSPO) is a mitochondrial molecule upregulated in microglia upon their activation. Positron emission tomography (PET) imaging using TSPO-binding radioligands provides a method to assess microglial activation in patients in vivo. In this mini-review, we summarize the current status of TSPO imaging in the field of MS. In addition, the review discusses new insights into the potential use of this method in treatment trials and in clinical assessment of progressive MS.

SUBMITTER: Airas L

PROVIDER: S-EPMC5879102 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography.

Airas Laura L Nylund Marjo M Rissanen Eero E

Frontiers in neurology 20180326

Understanding the mechanisms underlying progression in multiple sclerosis (MS) is one of the key elements contributing to the identification of appropriate therapeutic targets for this under-managed condition. In addition to plaque-related focal inflammatory pathology typical for relapsing remitting MS there are, in progressive MS, widespread diffuse alterations in brain areas outside the focal lesions. This diffuse pathology is tightly related to microglial activation and is co-localized with s ...[more]

PMID: 29632509

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography.

Publications

Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography.

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