Role of MHC Class I on ALS progression in 129Sv-G93A mice

• Grant number: 17/02895-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2017
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Gabriela Bortolança Chiarotto
• Supervisor: Caterina Bendotti
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Istituto di Ricerche Farmacologiche Mario Negri (IRCCS), Italy
• Associated to the scholarship: 13/16168-8 - Administration of riluzole, tempol and mesenchymal stem cells in the treatment of ALS in SOD1 G93A mice, BP.DR

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the motor system. The cause of the disease is still unknown, but some protein mutations have been linked to the pathological process. Previously, it has been considered that immune abnormalities might contribute to the pathogenesis of disease. However, more recently it has become apparent that the immune response can also generate a protective outcome. Importantly, expression of MHC I molecules by neurons has been shown to develop non-canonic roles, resulting in neuroprotection from activated astrocytes. In turn, upregulation of MHC I by motoneurons in vivo and in vitro, has proven to be neuroprotective. Such upregulation also results in significant improvement in G93A SOD 1 transgenic mice life span. Recent studies suggest a role for chemokines in the inflammatory process in ALS. These molecules are also important for the interaction between glial cells and neurons. Our aims in this project are to investigate mechanisms identified as responsible for the variability of the disease course in SOD1G93A mice, through the development of an accurate preclinical gene therapy. For this, we will develop adenoviral vectors to induce the expression of both CCL2 and MHCI by neurons and glial cells. Further, we will transfect the animals to evaluate the role of these molecules on ALS progression. Besides that, we will also evaluate the effect of overexpression of MHCI and/or CCL2 specifically by motoneurons on the survival and morphology in co-culture with astrocytes derived from SOD1G93A and non-transgenic mice. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; BISCOLA, NATALIA PERUSSI; SPEJO, ALINE BARROSO; GUBERT, FERNANDA; FRANCA JUNIOR, MARCONDES; MENDEZ-OTERO, ROSALIA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1(G93A)) of ALS. JOURNAL OF NEUROINFLAMMATION, v. 16, n. 1, NOV 14 2019. (13/16168-8, 17/02895-6, 18/05006-0, 14/06892-3)

CHIAROTTO, GABRIELA BORTOLANCA; NARDO, GIOVANNI; TROLESE, MARIA CHIARA; FRANCA, JR., MARCONDES CAVALCANTE; BENDOTTI, CATERINA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. The Emerging Role of the Major Histocompatibility Complex Class I in Amyotrophic Lateral Sclerosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 11, NOV 2017. (14/06892-3, 17/02895-6, 13/16168-8)