Characteristics of TSPO expression in marmoset EAE

Area of Science:

• Neuroimmunology
• Neuroinflammation
• Primate Models of Disease

Background:

• Multiple sclerosis (MS) is a significant cause of disability in young adults, characterized by central nervous system (CNS) inflammation and demyelination.
• The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and a positron emission tomography (PET) imaging target highly expressed in MS lesions, serving as an inflammatory biomarker and potential therapeutic target.
• The precise pathological role of TSPO in human MS remains incompletely understood.

Purpose of the Study:

• To characterize TSPO expression patterns in the common marmoset model of experimental autoimmune encephalomyelitis (EAE), a primate model of MS.
• To investigate the cellular localization and phenotypic association of TSPO in both control and EAE marmoset CNS tissues.
• To compare TSPO expression dynamics in acute and chronic EAE lesions to understand its evolving role in MS pathogenesis.

Main Methods:

• Multiplex immunofluorescence was employed to analyze fixed CNS tissues from control and EAE marmosets.
• TSPO expression was examined in relation to microglial (Iba1), astrocytic, and neuronal markers.
• Co-expression analysis with markers for antigen presentation (CD74), activation (MRP14), phagocytosis (CD163), and anti-inflammatory phenotype (Arg1) was performed.

Main Results:

• In control marmosets, TSPO was detected in leptomeninges, ependyma, and over two-thirds of microglia, but not in astrocytes or neurons.
• In both control and acute EAE, TSPO was co-expressed with various microglial activation and phenotype markers, indicating its presence across different microglial states.
• TSPO expression was high in activated microglia in acute EAE lesions (>88%), but significantly decreased in chronic lesions (<13%). Astrocytic TSPO expression increased in chronic lesions with astrogliosis, and neuronal TSPO expression was observed in a subset of glutamatergic neurons.

Conclusions:

• The marmoset EAE model exhibits dynamic TSPO expression patterns, with an initial high expression in microglia/macrophages that shifts towards astrocytes in chronic stages.
• These observed changes in TSPO expression, particularly the temporal shift between cell types, align with neuropathological findings in human MS.
• The marmoset EAE model is a relevant tool for studying TSPO's role in immune dysregulation relevant to human MS pathology.