RESUMO
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.
RESUMO
Administration of erythropoietin (EPO) is neuroprotective against a variety of experimentally-induced neurological disorders. The aim was to determine if EPO protects against hippocampal neurodegeneration as well as impairment of cognition and motor performance, associated with long-term diabetes. BALB/c mice were randomly allocated between control, diabetic and EPO-treated diabetic groups. EPO-treated diabetic mice were administered EPO 0.05 U/kg/day i.p. three times/week for 10 weeks. Cognition was assessed by Morris water maze. Brain samples were processed for light microscopic evaluation of hippocampus. Controls showed gradual improvement of cognitive performance in water maze when comparing latency (p < 0.01) and distance swum to reach the platform (p = 0.001). There was a similar trend for improvement in EPO-treated diabetics (p < 0.001). Latency did not improve in diabetic animals indicating lack of learning (p = 0.79). In probe trials, controls and EPO-treated diabetics spent more time in the training quadrant than expected by chance (p < 0.001). Diabetics did not show memory recall behavior; performance was significantly worse than expected by chance (p = 0.023). In diabetics, there was neurodegeneration in hippocampus and reduction in number of granule cells (p < 0.01) in the dentate gyrus. EPO treatment improved these neurodegenerative changes and preserved numbers of granule cells (p < 0.1, compared to controls). Erythropoietin treatment is protective against cognitive deficits and hippocampal neurodegeneration in diabetic mice.
