| Texto completo | |
| Autor(es): |
Tomiyama, Ana Laura M. R.
;
Cartarozzi, Luciana Politti
;
Coser, Liliande Oliveira
;
Chiarotto, Gabriela Bortolanca
;
Oliveira, Alexandre L. R.
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN CELLULAR NEUROSCIENCE; v. 17, p. 20-pg., 2023-08-30. |
| Resumo | |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that progressively affects motoneurons, causing muscle atrophy and evolving to death. Astrocytes inhibit the expression of MHC-I by neurons, contributing to a degenerative outcome. The present study verified the influence of interferon beta (IFN beta) treatment, a proinflammatory cytokine that upregulates MHC-I expression, in SOD1(G93A) transgenic mice. For that, 17 days old presymptomatic female mice were subjected to subcutaneous application of IFN beta (250, 1,000, and 10,000 IU) every other day for 20 days. Rotarod motor test, clinical score, and body weight assessment were conducted every third day throughout the treatment period. No significant intergroup variations were observed in such parameters during the pre-symptomatic phase. All mice were then euthanized, and the spinal cords collected for comparative analysis of motoneuron survival, reactive gliosis, synapse coverage, microglia morphology classification, cytokine analysis by flow cytometry, and RT-qPCR quantification of gene transcripts. Additionally, mice underwent Rotarod motor assessment, weight monitoring, and neurological scoring. The results show that IFN beta treatment led to an increase in the expression of MHC-I, which, even at the lowest dose (250 IU), resulted in a significant increase in neuronal survival in the ALS presymptomatic period which lasted until the onset of the disease. The treatment also influenced synaptic preservation by decreasing excitatory inputs and upregulating the expression of AMPA receptors by astrocytes. Microglial reactivity quantified by the integrated density of pixels did not decrease with treatment but showed a less activated morphology, coupled with polarization to an M1 profile. Disease progression upregulated gene transcripts for pro- and anti-inflammatory cytokines, and IFN beta treatment significantly decreased mRNA expression for IL4. Overall, the present results demonstrate that a low dosage of IFN beta shows therapeutic potential by increasing MHC-I expression, resulting in neuroprotection and immunomodulation. (AU) | |
| Processo FAPESP: | 18/05006-0 - Recuperação sensório-motora após axotomia de raízes medulares: emprego de diferentes abordagens experimentais |
| Beneficiário: | Alexandre Leite Rodrigues de Oliveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 20/15892-8 - Emprego do Interferon beta e do 4-hidroxy-tempo no tratamento da Esclerose Lateral Amiotrófica em camundongos SOD1G93A |
| Beneficiário: | Ana Laura Midori Rossi Tomiyama |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |