Cognitive impairment in a murine model of experimental autoimmune encephalomyelitis with relapsing-remitting course

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disorder characterized by demyelination and progressive axonal loss that affects the central nervous system. In addition of physical disability and the neurodegenerative process, MS associates with co-morbid behavioral, neuropsychiatric and cognitive impairment, including learning and memory deficits. The study of cognitive impairment in the currently most suitable experimental animal model of MS, experimental autoimmune encephalomyelitis (EAE), constitutes a very valuable tool to translate ultimately into clinical a better diagnosis and more effective treatment protocols. In our study, we analyzed the behavioral profile of a murine model of EAE induced by myelin oligodendrocyte glycoprotein peptide (MOG35-55) which develops a relapsing-remitting course. In the early neuroinflammatory phase of the disease, i.e. 19-21 days post immunization (dpi), EAE mice exhibited deficits in motor coordination/skill learning (Rotarod test), and spatial working memory (spontaneous alternation in Y-maze), as well as depressive symptoms (tail suspension test) and anxiety-like behavior (elevated plus-maze). EAE mice did not yet show object recognition memory impairments, suggesting that reference memory was not altered in this phase. However, from 33-35 dpi until late phases (49-52 dpi), independently of clinical score, EAE mice exhibited a memory decline showing lower discrimination index in the object recognition test. EAE late phase was also characterized by motor coordination and spatial working memory impairments as well as higher anxiety-like behavior. Overall, these data demonstrates a differential pattern of gradual cognitive dysfunctions during the relapsing-remitting EAE course that could help to understand the development of progressive cognitive decline in MS patients.

Funding: Andalusian Regional Ministries of Economy, Innovation, Science and Employment (SEJ-1863; CTS643) and of Health (PI-0234-2013; Nicola´s Monardes Programme).