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Title: Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice
Author: Griñán Ferré, Christian
Sarroca, Sara
Ivanova, Aleksandra
Puigoriol Illamola, Dolors
Aguado Tomàs, Fernando
Camins Espuny, Antoni
Sanfeliu i Pujol, Coral
Pallàs i Llibería, Mercè, 1964-
Keywords: Malaltia d'Alzheimer
Malalties neurodegeneratives
Alzheimer's disease
Neurodegenerative diseases
Issue Date: 21-Mar-2016
Publisher: Impact Journals
Abstract: 5XFAD is an early-onset mouse transgenic model of Alzheimer disease (AD). Up to now there are no studies that focus on the epigenetic changes produced as a result of Aβ-42 accumulation and the possible involvement in the different expression of related AD-genes. Under several behavioral and cognition test, we found impairment in memory and psychoemotional changes in female 5XFAD mice in reference to wild type that worsens with age. Cognitive changes correlated with alterations on protein level analysis and gene expression of markers related with tau aberrant phosphorylation, amyloidogenic pathway (APP, BACE1), Oxidative Stress (iNOS, Aldh2) and inflammation (astrogliosis, TNF-α and IL-6); no changes were found in non-amyloidogenic pathway indicators such as ADAM10. Epigenetics changes as higher CpG methylation and transcriptional changes in DNA methyltransferases (DNMTs) family were found. Dnmt1 increases in younger 5XFAD and Dnmt3a and b high levels in the oldest transgenic mice. Similar pattern was found with histone methyltransferases such as Jarid1a andG9a. Histone deacetylase 2 (Hdac2) or Sirt6, both related with cognition and memory, presented a similar pattern. Taken together, these hallmarks presented by the 5XFAD model prompted its use in assessing different potential therapeutic interventions based on epigenetic targets after earlier amyloid deposition.
Note: Reproducció del document publicat a:
It is part of: Aging, 2016, vol. 8, num. 4, p. 664-684
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ISSN: 1945-4589
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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