Dose-Response Relationship of EAE Clinical Severity in a MOG35-55 Mouse Model: A Pilot Study

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a common animal model of multiple sclerosis (MS) which mimics the autoimmune, demyelinating, and inflammatory hallmarks of this human disorder. To better understand the severity of the symptoms in relation to the antigen in EAE, we explored the dose-symptom relationship between the quantity of MOG35-55 and clinical symptoms in a C57/BL6 mouse pilot study. To isolate the impact of MOG35-55 we developed an EAE model that does not require the additional application of pertussis toxin. Mice were treated with either 50µg, 100µg, or 150µg of MOG35-55 emulsified in complete Freund’s adjuvant. Following induction, the mice were assessed for clinical symptoms daily, and tested weekly for gross and fine motor impairments, mechanical allodynia, and anxiety-like behaviours. The time course of sensorimotor function loss was characterized by multiphasic disease progression. Findings also suggested an inverted U-shape dose-response relationship with a medium dosage of 100 µl MOG35-55 dosage aggravating symptom severity in induced animals. Outcomes measured by a clinical score correlated with performance on motor and nociceptive sensitivity tasks. As the disease progressed, fine and gross motor impairments and nociceptive sensitivity diminished and impairments persisted beyond 8 weeks. This study indicates that mild to moderate EAE can be induced in the absence of use of pertussis toxin. The progression suggests a spontaneously multiphasic disease course, which may have attractive implications for clinically relevant animal models.