Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis

Autor(es)

Chaves-Filho, Adriano Britto ^[1] ; Dantas Pinto, Isabella Fernanda ^[1] ; Dantas, Lucas Souza ^[1] ; Xavier, Andre Machado ^[2] ; Inague, Alex ^[1] ; Faria, Rodrigo Lucas ^[1] ; Medeiros, Marisa H. G. ^[1] ; Glezer, Isaias ^[2] ; Yoshinaga, Marcos Yukio ^[1] ; Miyamoto, Sayuri ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, AUG 12 2019.
• Citações Web of Science: 0

Resumo

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons leading to muscle paralysis and death. While a link between dysregulated lipid metabolism and ALS has been proposed, lipidome alterations involved in disease progression are still understudied. Using a rodent model of ALS overexpressing mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A), we performed a comparative lipidomic analysis in motor cortex and spinal cord tissues of SOD1-G93A and WT rats at asymptomatic (similar to 70 days) and symptomatic stages (similar to 120 days). Interestingly, lipidome alterations in motor cortex were mostly related to age than ALS. In contrast, drastic changes were observed in spinal cord of SOD1-G93A 120d group, including decreased levels of cardiolipin and a 6-fold increase in several cholesteryl esters linked to polyunsaturated fatty acids. Consistent with previous studies, our findings suggest abnormal mitochondria in motor neurons and lipid droplets accumulation in aberrant astrocytes. Although the mechanism leading to cholesteryl esters accumulation remains to be established, we postulate a hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress. Implicated in the pathology of other neurodegenerative diseases, cholesteryl esters appear as attractive targets for further investigations. (AU)

• Processo FAPESP: 18/18633-3 - Sinalização e Modificação Lipídica via Receptor CD36 no Sistema Nervoso
• Beneficiário: Isaias Glezer
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 10/50891-0 - Ácido docosahexaenóico e colesterol: caracterização e detecção de produtos de oxidação, modificação de proteínas e implicações na esclerose lateral amiotrófica
• Beneficiário: Sayuri Miyamoto
• Modalidade de apoio: Auxílio à Pesquisa - Regular