Pathology and pathogenesis of MS - Experimental models

ERHARDT BRENDA; FERNANDO J PITOSSI; MARIA CELESTE LEAL; CARINA C FERRARI; BERENICE ANABEL SILVA; FARIAS, MARIA I.

Estocolmo

Congreso; CONGRESO ECTRIMS (EUROPEAN COMMITTE FOR TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS),; 2019

EUROPEAN COMMITTE FOR TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS

Background: The beneficial effects of environmental enrichment (EE) were demonstrated in a few multiple sclerosis (MS) animal models, with main focus on white matter lesions. EE evaluates three enrichment paradigms: social interaction, cognitive and physical stimulation. Additionally, it is known that, the combination of both cognitive and physical activities enhances the cognitive performance in MS patients. Our group created a focal chronic cortical MS animal model which present cognitive impairment, depression, anxiety-like symptoms, along with neuroinflammation, neurodegeneration and demyelination that lasts for 50 days (Silva et al., 2018)Aims: The aim of this work is to study the influence of EE in focal cortical lesions induced by central and peripheral expression of interleukin 1 beta (IL-1b).Material and Methods. Adult rats were injected both in the cortex and in the periphery with an adenovirus expressing IL-1b. The animals were distributed in either enriched environment or standard cages (SC) for 30 days. We performed behavioural tests, immunohistochemical and molecular biology analyses of peripheral blood and cortical lesions.Results: EE ameliorates depression, anxiety like-symptoms and short term memory impairment. Additionally, EE decreases central and peripheral inflammation and astroglia activation along with a diminished demyelination in EE animals compared to SC animals. Moreover, central production of pro-inflammatory cytokines IL-1b, interleukin 6 and tumoral necrosis factor α are diminished; meanwhile the expression of anti-inflammatory molecules arginase 1, transforming growth factor β and brain derived neurotrophic factor, are increased.Conclusions: Environmental enrichment ameliorates cortical and peripheral inflammation and improves behavioural and cognitive function. It also induces microglia polarization and neurotrophin production. Therefore, EE may act synergistically with other therapeutic agents to facilitate brain repair and general welfare.Disclosure: There are no conflicts of interest of these authors for this work