Effects of enhanced environment and induced depression on cuprizone mouse model of demyelination

Impairment in cognition and motor activity are commonly encountered in patients affected by multiple sclerosis (MS), and depression is believed to be a contributing factor. The aim of the present study was to investigate the impact of induced depression on a cuprizone mouse model of demyelination and the effectiveness of enhanced environment (EE) as a method of intervention. C57BL/6 male mice were divided into five groups: Cuprizone only (Cup-O), cuprizone undergoing depression (Cup-Dep), cuprizone housed in EE (Cup-EE), cuprizone housed in EE and undergoing depression (Cup-ED) and the control (n=9-10 per group). Depression was induced by repeated open-space forced swim. Neurobehavioral tests were conducted following a 6-week period of 0.2% cuprizone-enriched diet. The Cup-EE group performed significantly better in terms of cognition and motor functions, when compared with the Cup-O group, as evidenced by the Morris water maze (MWM; P<0.001) and rotarod performance test (P<0.05) results. Conversely, the Cup-Dep group exhibited a significant decline in performance in the MWM (P<0.001) and rotarod performance test (P<0.05), when compared with the Cup-O group. The Cup-ED group had comparable results to those of the Cup-O group, indicating a reversal of the induced depression effects. Open field test results failed to show an anxiety-like behavior in the cuprizone mouse model. It was therefore concluded that EE can improve MS-associated cognitive and motor deficits. Insights gained from these results facilitate the exploration of non-medical modes of intervention as an emerging adjuvant therapy in MS.