Biomarcadores para progressão da distrofia muscular de Duchenne: impacto da idade no músculo protegido da língua de mdx.

• Processo: 23/12417-5
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Data de Início da vigência: 01 de outubro de 2023
• Data de Término da vigência: 31 de março de 2024
• Área do conhecimento: Ciências Biológicas - Biologia Geral
• Pesquisador responsável: Cintia Yuri Matsumura
• Beneficiário: Cintia Yuri Matsumura
• Instituição Sede: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brasil
• Assunto(s): Biomarcadores Camundongos endogâmicos mdx Distrofia muscular de Duchenne Língua Metaboloma Músculo esquelético
• Palavra(s)-Chave do Pesquisador: biomarcadores | Camundongos Mdx | Degeneração e proteção muscular | Distrofia Muscular de Duchenne | língua | Metaboloma | Músculo esquelético

Resumo

Background: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-± and TGF-², are potential biomarkers for dystrophic muscle characterization. Methods: To investigate disease progression and aging, we utilized young (1-month old) and old (21-25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1-H Nuclear Magnetic Resonance, while TNF-± and TGF-² were assessed using Western blotting to examine inflammation, and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. Results: The histological analysis of the tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild type or mdx tongues of the same age. The metabolites alanine, methionine, 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine and the proteins TNF-± and TGF-² had no difference in the analysis between groups (p > 0.05).Conclusions: Surprisingly, histological, metabolite, and protein analysis reveals that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-±, and TGF-² do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging. (AU)