Analysis of the effect of Low-Level Laser Therapy on chronic demyelination induced by cuprizone

• Grant number: 19/08075-6
• Support type: Regular Research Grants
• Duration: April 01, 2021 - March 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal researcher: Gláucia Monteiro de Castro
• Grantee: Gláucia Monteiro de Castro
• Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Assoc. researchers: Ana Claudia Muniz Renno

Abstract

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). It is probably caused by an autoimmune response in which the inflammatory process destroys the myelin sheath. The main feature of MS is demyelinated lesions that create an environment preventing access of oligodendrocyte precursor cells (OPCs), and their survival and differentiation. Over time, remyelination fails, especially in chronic lesions. The absence of effective therapies has driven the search for alternative treatments for MS and other demyelinating diseases. There are several studies demonstrating the positive effects of photobiomodulation (or Low-Level Laser Therapy - LLLT) in the CNS. Our group has demonstrated that the use of LLLT on models of spinal cord injury and acute demyelination, improves tissue regeneration, inflammatory response and, consequently, performance in functional tests. The proposed work aims to investigate the efficacy and mechanisms involved in the effect of low-level laser treatment in animals submitted to chronic demyelination induced by cuprizone. We will use C57BL / 6 mice, distributed in 4 groups: CTL (control), CTLL (laser control), CPZ (cuprizone) and CPZL (laser cuprizone). Functional tests will be carried out to monitor demyelination and treatment. After euthanasia, proliferation and differentiation of oligodendrocyte precursor cells will be evaluated, and the effective remyelination occurring in the corpus callosum will be determined by transmission electron microscopy. We will scrutinise the mechanisms involved in the demyelination process and the effects of LLLT on remyelination through the study of the transcriptome, analysis of mitochondrial integrity and mitochondrial membrane potential, the study of expression of proteins involved in the endoplasmic reticulum stress and apoptosis. In this way, we expect to clarify the mechanisms involved in the effects of laser therapy on the induction of remyelination in a model of irreversible chronic demyelination induced by cuprizone. (AU)