Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1G93A) of ALS.

Autor:	Chiarotto, Gabriela Bortolança, Cartarozzi, Luciana Politti, Perez, Matheus, Biscola, Natalia Perussi, Spejo, Aline Barroso, Gubert, Fernanda, França Junior, Marcondes, Mendez-Otero, Rosália, de Oliveira, Alexandre Leite Rodrigues
Předmět:	INFLAMMATION AMYOTROPHIC lateral sclerosis DELAYED onset of disease BEHAVIORAL assessment TRANSMISSION electron microscopy SPINAL cord BIOLOGICAL models ANIMAL experimentation INTERLEUKIN-1 CELL physiology NEUROPROTECTIVE agents OXIDES TUMOR necrosis factors RESEARCH funding FREE radicals MOTOR ability MOTOR neurons MICE PHARMACODYNAMICS
Zdroj:	Journal of Neuroinflammation; 11/14/2019, Vol. 16 Issue 1, pN.PAG-N.PAG, 1p
Abstrakt:	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 SOD1G93A 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 (IL1β and TNFα) and a three-fold decrease in the expression of TGFβ1 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 SOD1G93A mice. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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