microRNAs expression correlates with levels of APP, DYRK1A, hyperphosphorylated Tau and BDNF in the hippocampus of a mouse model for Down syndrome during ageing

Autor(es)

Chaves, Juliana C. S. ^[1] ; Machado, Felippe T. ^[1] ; Almeida, Michael F. ^[1] ; Bacovsky, Tatiana B. ^[1] ; Ferrari, Merari F. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet Biol & Evolut, Rua Matao 277, Cidade Univ, BR-05508090 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience Letters; v. 714, JAN 1 2020.
• Citações Web of Science: 0

Resumo

Down syndrome (DS) patients are more susceptible to Alzheimer's disease (AD) due to the presence of three copies of genes on chromosome 21 such as DYRK1A, which encodes a broad acting kinase, and APP (amyloid precursor protein), leading to formation of amyloid beta (A beta) peptide and hyperphosphorylation of Tau. In this study, we investigated the association among miRNAs miR-17, -20a, -101, -106b, -199b, -26a, 26b and some of their target mRNAs such as APP, DYRK1A and BDNF, as well as the levels of hyperphosphorylated Tau in the hippocampus of a 2 and 5 months old mice model of trisomy 21 (Ts65Dn). Results indicated that increased APP expression in the hippocampus of 5-months old DS mice might be correlated with decrease in miR-17, -20a, -101 and -106b. Whereas at 2 months of age normal levels of APP expression in the hippocampus was correlated with increased levels of miR-17, -101 and -106b in DS mice. DYRK1A mRNA also increased in the hippocampus of 5 months old DS mice and it is associated with decreased levels of miR-199b. Increased levels of DYRK1A in 5-month old mice are associated with increased phosphorylation of Tau at Thr212 residue but not at Ser199-202. Tau pathology is accompanied by decreased expression of BDNF and increased miR-26a/b in mice of 5 months of age. Taken together, data indicate that miR-17, -20a, -26a/b, -101, -106b and -199b might be interesting targets to mitigate Tau and A beta pathology in DS. (AU)

• Processo FAPESP: 18/07592-4 - Papel dos mecanismos de controle de qualidade na perda da proteostase em doenças neurodegenerativas dependentes da idade
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18961-2 - Estudo da autofagia como mecanismo para o desencadeamento de doenças neurodegenerativas
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/10892-1 - Estudo dos mecanismos inflamatórios mediados por receptores da imunidade inata na esclerose lateral amiotrófica
• Beneficiário: Renato Barboza
• Modalidade de apoio: Auxílio à Pesquisa - Regular