Administration of riluzole, tempol and mesenchymal stem cells in the treatment of ALS in SOD1 G93A mice

• Grant number: 13/16168-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2014
• End date: February 02, 2018
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Gabriela Bortolança Chiarotto
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 17/02895-6 - Role of MHC Class I on ALS progression in 129Sv-G93A mice, BE.EP.DR

Abstract

The amyotrophic lateral sclerosis is a neurodegenerative disease characterized by selective loss of motor neurons in the spinal cord, brainstem and motor cortex. It is possible that, similar than occurs in other neurodegenerative diseases, the pathological mechanism underlying ALS is a set of cellular and biochemical alterations that ultimately trigger the degeneration of motor neurons. The treatment is mainly based on symptomatic measures and pharmacological therapy with riluzole is not curative. Thus, it is of utmost importance the development of new therapeutic strategies. Alternatively, there is the prospect of using cyclic nitroxides such as Tempol, since they are multifunctional antioxidants that have low toxicity in experimental animals. Another option is a stem cell therapy to replace degenerating neurons, or prevent / delay the process of neuronal death. The objective of this study is to verify if the interaction between riluzole, tempol and mesenchymal stem cells have therapeutic potential in SOD1 G93A transgenic mice. Treatment with riluzole (8mg/kg), Tempol (24mg/kg) and mesenchymal stem cells will start at 70 days of life transgenic animals. Animal control will receive saline as a vehicle. To determine the age of onset of the disease and differences in the progression will be used Rotarod motor test and body weight of the animals. The survival of animals will also be analyzed. After euthanasia, samples will be processed for the realization of the following techniques: Nissl staining, immunohistochemistry, transmission electron microscopy and qRT-PCR. (AU)

Scientific publications

(4)

(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)

SPEJO, A. B.; CHIAROTTO, G. B.; FERREIRA, A. D. F.; GOMES, D. A.; FERREIRA JR, R. S.; BARRAVIERA, B.; OLIVEIRA, A. L. R.. Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells. JOURNAL OF NEUROINFLAMMATION, v. 15, AUG 14 2018. (14/06892-3, 12/22750-9, 13/16168-8)

CHIAROTTO, GABRIELA BORTOLANCA; CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; TOMIYAMA, ANA LAURA MIDORI ROSSI; DE CASTRO, MATEUS VIDIGAL; DUARTE, ADRIANA S. S.; LUZO, ANGELA CRISTINA MALHEIROS; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Delayed onset, immunomodulation, and lifespan improvement of SOD1G93A mice after intravenous injection of human mesenchymal stem cells derived from adipose tissue. Brain Research Bulletin, v. 186, p. 12-pg., 2022-08-01. (18/05006-0, 13/16168-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CHIAROTTO, Gabriela Bortolança. Administration of riluzole, tempol and mesenchymal stem cells in treatment of ALS in SOD1G93A mice. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.