EVALUATION OF THE ELECTRONEUROMYOGRAPHIC RESPONSE AFTER TREATMENT WITH INTERFERON BETA IN SOD1G93A TRANSGENIC MICE.

• Grant number: 23/08562-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Julia Freitas da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a disease characterized by the degeneration of motor neurons, resulting in muscle weakness and atrophy, fasciculations, progressive paralysis, and speech and swallowing impairments. Death occurs two to five years after the onset of symptoms, usually due to respiratory failure. ALS is classified into two main types: familial, of hereditary origin, and sporadic, which has an unknown etiology. Both are caused by genetic mutations, which differ in their origin, however, all their pathological characteristics are equivalent. Studies demonstrate that astrocytes, cells responsible for metabolic support and removal of excess glutamate from the synaptic cleft, in ALS cases, change their profile and start to exert toxic effects on motor neurons. Furthermore, it has already been reported that astrocytes, derived from mice with ALS, lead to a decrease in the expression of the MHC-I molecule. This typical molecule of the immune system contributes to the development, plasticity, and protection of the nervous system. In ALS cases, its expression is reduced, preventing it from exercising its neuroprotective role in the neuronal body as well as in axons and neuromuscular junctions. With this in mind, the present study aims to analyze whether treatment with Interferon ² is capable of preserving the neuromuscular junctions of the hindlimbs, from the characteristic toxicity of ALS, through the expression of MHC-I, in SOD1G93A transgenic mice. For this, the animals will be treated with IFN², at a dose of 250UI, on alternate days, from 70 (pre-symptomatic) days of life to 90 (onset of the disease) and 100 days (chronic phase). To evaluate the neuromuscular response, the electroneuromyography technique will be used. Additionally, at the end of treatment, the animals will be euthanized and their sciatic nerves will be collected for morphological analysis and immunostained with anti-neurofilaments and S100, to analyze axonal preservation and Schwann cell reactivity.