An investigation of the effect of cuprizone-induced demyelination using histological, behavioural, proteomics and immunological approaches

Abstract

Feeding cuprizone (CPZ) to animals has been long known to lead to regional degeneration of oligodendrocytes (OLG) and has been used to model the demyelinating aspect of human conditions like multiple sclerosis (MS). The MS aetiology is unknown and no single animal model faithfully replicates the myriad of symptoms. Currently, there are two competing hypotheses regarding the pathophysiology underlying the initiation of MS: 'outside-in' and'inside-out'. In this thesis, the broad objective was to develop an animal model of progressive demyelination reminiscent to MS. CPZ was used to induce OLG degeneration (termed oligodendrocytosis) and pertussis toxin (PT) was used to breach blood brain barrier (BBB) in order to test whether demyelination within the brain when combined with a breach of the BBB could trigger an adaptive immune response in the brain and thereby provide new evidence for an 'inside-out' hypothesis. The second broad aim was to investigate sensorimotor behavioural deficits and associated regulating pathways to find a link between CPZ-induced behavioural deficits and MS clinical symptoms. The results of the present thesis are presented in the following published manuscripts.

Date of Award	2019
Original language	English