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Published on: February 1, 2019
Monitoring of EAE onset and progression in the common marmoset monkey by sequential high-resolution 3D MRI
Susann Boretius1, Barthel Schmelting, Takashi Watanabe
1Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für Biophysikalische Chemie, 37070 Göttingen, Germany. sboreti@gwdg.de
Abstract:
Experimental autoimmune encephalomyelitis (EAE) induced by myelin-oligodendrocyte glycoprotein (MOG) in common marmosets (Callithrix jacchus) is a model for multiple sclerosis. Here, EAE was induced in four common marmosets by 250-300 microg recombinant rat MOG. In addition to a detailed disability scoring, T2- and T1-weighted high-resolution 3D MRI was performed to assess the onset and development of cerebral lesions. The findings were confirmed by histopathology in all animals. Although the animals exhibited a large heterogeneity with regard to onset and localization of lesions and also to disease duration and severity of disability signs, none of the animals revealed any evidence of recovery. A specification of the disability scoring system to account for different aspects of the disease led to a good concurrence of the first MRI-detectable lesion and the onset of central nervous system (CNS) symptoms. The results suggest that MRI monitoring of white matter lesions in conjunction with disability scores that focus on CNS symptoms may be a suitable method to evaluate novel therapeutic interventions even in the presence of pronounced interindividual heterogeneity.
Insights
Experimental autoimmune encephalomyelitis (EAE) in marmosets, induced by myelin-oligodendrocyte glycoprotein (MOG), serves as a multiple sclerosis model. MRI and disability scoring effectively track disease progression, aiding therapeutic evaluation.
Area of Science:
- Neuroscience
- Immunology
- Primate Models
Background:
- Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS).
- Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model to study MS pathogenesis.
- Myelin-oligodendrocyte glycoprotein (MOG) is a key autoantigen in EAE induction.
Purpose of the Study:
- To establish and characterize a novel model of EAE in common marmosets (Callithrix jacchus) induced by MOG.
- To assess the utility of magnetic resonance imaging (MRI) and detailed clinical scoring for monitoring disease progression in this model.
- To evaluate the potential of this marmoset EAE model for preclinical testing of therapeutic interventions.
Main Methods:
- Induction of EAE in common marmosets using recombinant rat MOG.
- High-resolution 3D T1- and T2-weighted MRI for cerebral lesion detection and characterization.
- Detailed neurological disability scoring system tailored to CNS symptoms.
- Histopathological confirmation of MRI findings.
Main Results:
- Successful induction of EAE in all marmosets, characterized by cerebral lesions and neurological deficits.
- Significant interindividual heterogeneity in disease onset, lesion localization, duration, and severity was observed.
- MRI detected cerebral white matter lesions correlating well with the onset of CNS symptoms.
- No spontaneous recovery was observed during the study period.
Conclusions:
- Marmoset EAE induced by MOG is a relevant preclinical model for multiple sclerosis.
- Combined MRI monitoring and refined disability scoring provide a robust method for tracking disease.
- This model's heterogeneity and sensitivity to early changes make it suitable for evaluating novel therapeutic strategies.
