Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1(G93A)) of ALS

Author(s)

Chiarotto, Gabriela Bortolanca ^[1] ; Cartarozzi, Luciana Politti ^[1] ; Perez, Matheus ^[1] ; Biscola, Natalia Perussi ^[2] ; Spejo, Aline Barroso ^[1] ; Gubert, Fernanda ^[3] ; Franca Junior, Marcondes ^[4] ; Mendez-Otero, Rosalia ^[3] ; Rodrigues de Oliveira, Alexandre Leite ^{[1, 5]}

Affiliation

^[1] Inst Biol Unicamp, Dept Struct & Funct Biol, BR-13083865 Campinas, SP - Brazil

^[2] UCLA, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 - USA

^[3] Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Biofis Carlos Chagas Filho, Sala G2-028, Cidade Univ, BR-21941902 Rio De Janeiro, RJ - Brazil

^[4] Fac Med Sci Unicamp, Dept Neurol, BR-13083887 Campinas, SP - Brazil

^[5] Univ Campinas UNICAMP, Lab Nerve Regenerat, Cidade Univ Zeferino Vaz, Rua Monteiro Lobato 255, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEUROINFLAMMATION; v. 16, n. 1 NOV 14 2019.
• Web of Science Citations: 0

Abstract

Background The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50 mg/kg) presents therapeutic potential in SOD1(G93A) transgenic mice. Methods Tempol treatment began at the asymptomatic phase of the disease (10th week) and was administered every other day until week 14, after which it was administered twice a week until the final stage of the disease. The animals were sacrificed at week 14 (initial stage of symptoms-ISS) and at the end stage (ES) of the disease. The lumbar spinal cord of the animals was dissected and processed for use in the following techniques: Nissl staining to evaluate neuronal survival; immunohistochemistry to evaluate astrogliosis and microgliosis (ISS and ES); qRT-PCR to evaluate the expression of neurotrophic factors and pro-inflammatory cytokines (ISS); and transmission electron microscopy to evaluate the alpha-motoneurons (ES). Behavioral analyses considering the survival of animals, bodyweight loss, and Rotarod motor performance test started on week 10 and were performed every 3 days until the end-stage of the disease. Results The results revealed that treatment with tempol promoted greater neuronal survival (23%) at ISS compared to untreated animals, which was maintained until ES. The intense reactivity of astrocytes and microglia observed in vehicle animals was reduced in the lumbar spinal cords of the animals treated with tempol. In addition, the groups treated with tempol showed reduced expression of proinflammatory cytokines (IL1 beta and TNF alpha) and a three-fold decrease in the expression of TGF beta 1 at ISS compared with the group treated with vehicle. Conclusions Altogether, our results indicate that treatment with tempol has beneficial effects, delaying the onset of the disease by enhancing neuronal survival and decreasing glial cell reactivity during ALS progression in SOD1(G93A) mice. (AU)

• FAPESP's process: 13/16168-8 - Administration of riluzole, tempol and mesenchymal stem cells in the treatment of ALS in SOD1 G93A mice
• Grantee: Gabriela Bortolança Chiarotto
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/02895-6 - Role of MHC Class I on ALS progression in 129Sv-G93A mice
• Grantee: Gabriela Bortolança Chiarotto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants