Neuroprotection by increased expression of the Major Histocompatibility Complex Class I (MHC i) in the nervous system of SOD1G93A mice

• Grant number: 19/16372-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Ana Laura Midori Rossi Tomiyama
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects motor neurons progressively, causing progressive weakness and muscle atrophy, leading to death frequently due to respiratory arrest. ALS can be classified into two main types, which differ in etiology. The familial type has a hereditary origin, while sporadic type represents the vast majority of cases (90%), and remains with its unknown etiology. In both types, the clinical signs are consequences of mutations that result in the motoneurons degeneration. The neuronal environment changes and the astrocytes of patients with ALS show some toxicity to the motoneurons themselves. It has also been observed that the MHC class I (MHC I) expression, a molecule with a classical function in the immune system, but which also plays a role in the nervous system, decreases. Astrocytes are supposed to inhibit MHC I, preventing from playing any neuroprotective role. According to this, the present study aims to verify the influence of treatment with Interferon beta, a proinflammatory cytokine known to induce an increase in MHC I expression, neuronal survival of motoneurons and glial reactivity in transgenic mice SOD1G93A. For this, daily doses (250, 500 and 1000 IU) will be administered from 70 days of life, with the animals sacrificed at the beginning of the symptomatic period of the disease (90 days). Thus, the spinal cord of the experimental groups will be collected for comparative analysis by RT-PCR, immunohistochemistry (gliosis and synaptic preservation) and Nissl staining (neuronal survival). Additionally, the experimental groups will undergo motor evaluation on the Rotarod appliance during the treatment period.