Targeting S1P receptors in experimental autoimmune encephalomyelitis in mice improves early deficits in locomotor activity and increases ultrasonic vocalisations.

Graham K Sheridan,Kumlesh K Dev

doi:10.1038/srep05051

Abstract

Fingolimod (FTY720) is an oral therapy for relapsing remitting multiple sclerosis (MS) and targets sphingosine 1-phosphate receptors (S1PRs). FTY720 also rescues animals from experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effects of FTY720 in EAE are primarily scored manually by examining weight loss and limb paralysis that begins around 10–12 days after immunisation. To our knowledge, pre-clinical effects of FTY720 on animal behaviour early in EAE have not been explored. Here, we developed an automated behaviour monitoring system to examine the early effects of FTY720 on subtle pre-symptomatic behaviour of mice induced with EAE. Our automated home-cage monitoring system (AHC-MS) enabled non-contact detection of movement and ultrasonic vocalisations (USVs) of mice induced with EAE, thus allowing detection of subtle changes in mouse behaviour before paralysis occurs. Mice receiving FTY720 emit longer USVs and display higher levels of motor activity than vehicle-treated EAE mice before clinical symptoms become apparent. Importantly, this study promotes the 3Rs ethics (replacement, reduction and refinement) in the EAE animal model and may also improve pre-screening of potentially novel MS therapies. In addition, this is the first report showing the early effects of FTY720 in EAE which underscores its protective effects.

Highlights

Targeting S1P receptors in experimental autoimmune encephalomyelitis in mice improves early deficits in locomotor activity and increases ultrasonic vocalisations
We developed an automated behaviour monitoring system to examine the early effects of FTY720 on subtle pre-symptomatic behaviour of mice induced with EAE
Our automated home-cage monitoring system (AHC-multiple sclerosis (MS)) enabled non-contact detection of movement and ultrasonic vocalisations (USVs) of mice induced with EAE, allowing detection of subtle changes in mouse behaviour before paralysis occurs

Summary

Introduction

Targeting S1P receptors in experimental autoimmune encephalomyelitis in mice improves early deficits in locomotor activity and increases ultrasonic vocalisations. Fingolimod (FTY720) is an oral therapy for relapsing remitting multiple sclerosis (MS) and targets sphingosine 1-phosphate receptors (S1PRs). This study promotes the 3Rs ethics (replacement, reduction and refinement) in the EAE animal model and may improve pre-screening of potentially novel MS therapies This is the first report showing the early effects of FTY720 in EAE which underscores its protective effects. Handling can affect experimental results[34], for example where stress can raise corticosterone levels in animals, which can alter EAE disease progression[35,36,37,38] Using this clinical scoring system, animals generally reach high disease scores before the beneficial effects of therapies can be assessed[39,40]

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