Behavioural correlates of experimental autoimmune encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system induced in laboratory rodents to mimic human demyelinating diseases such as multiple sclerosis (MS). This thesis applies EAE to studies in behavioural neuroscience by first establishing a literature review of physical and behavioural deficits in various EAE rodent models. Experiment 1 focuses on developing a comprehensive behavioural profile of EAE using a monophasic model of disease in Lewis (LEW) rats immunized with myelin basic protein (MBP). In this experiment, three commonly used EAE assessment scales were compared to determine which scale was the most sensitive to EAE changes. In addition physical and behavioural tasks were used to establish a temporal profile of skilled walking, anxiety, fatigue, and allodynia in EAE rats. In Experiment 2, the influence of chronic stress on the clinical disease course of monophasic MBP-EAE in LEW rats was investigated. Additionally, a longitudinal profile of physical and behavioural symptoms of EAE influenced by chronic stress was established. Furthermore, Experiments 2 and 3 utilized the expression of immune markers, epigenetic changes, and trace element analysis to develop an understanding of the mechanisms behind EAE and the role of chronic stress in this disease. The discussion section of this thesis closes with a summary on the use of LEW rats in these experiments. In addition, a protocol on the methods and troubleshooting of EAE immunizations is presented.