Analyses of the Metallothioneis I, II and III expression in the demyelination cuprizone-induced in Lewis rat strain

• Grant number: 09/14592-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2009
• End date: November 30, 2010
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Carolina Prado de França Carvalho
• Grantee: Sabine Nunes Boilesen
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

The multiple sclerosis is a chronic, demyelinating disease of the central nervous system (CNS), which the relapse-remitting course leads to cognitive and motor impairment. The knowledge about the pathogenesis of the multiple sclerosis has been clarified from studies carried with experimental models, as the experimental autoimmune encephalomyelitis (EAE), which depends on genetically susceptible animals. The Lewis rat strain is highly susceptible to autoimmunity because exhibit a failure in the hypothalamus-pituitary-adrenal axis leading to reduced plasma corticotrophin release from the pituitary and corticosterone from the adrenal cortex. The demyelination induced by the different EAE paradigms or virus, was characterized by sporadic, inconsistent and sparse, making the injury analyzes difficult by the lack of anatomical reproducibility and by the variability of animal strain used. During the demyelination process, have been showing the upregulation of antioxidant genes, like the metallothioneins, which have been related with the regeneration and remyelination process. The aim of this project is to evaluate the chronic demyelination cuprizone-induced in Lewis rats, related to the inflammatory response and this effect on the lipidic metabolism through the molecular, morphologic and biochemistry analyses. The treatment with cuprizone will be analyzed through the morphologic study of the CNS, submitted to Luxol Fast Blue stain to verify the demyelination process in the corpus callosum, superior cerebellar peduncles and in the cortex and by determination of whole myelin. The inflammatory process will be evaluated of the Metallothioneins I, II and III by RT-PCR and ELISA. The aim of the present project is to establish a possible relationship between the demyelination, inflammatory process, and the metallothioneins expression associated to a demyelination process cuprizone-induced in Lewis rat.