title: Age-dependent increment of hydroxymethylation in the brain cortex in the triple-transgenic mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a complex disorder whose etiology is associated with environmental and genetic factors. Recently there have been several attempts to analyze the role of epigenetic alterations in the origin and progression of this neurodegenerative condition. To evaluate the potential participation of the methylation status of the genome that may contribute to AD progression, we have studied the levels and distribution of the 5-methylcytosine and 5-hydroxymethylcytosine in different brain regions at different ages. We analyzed and quantified the immunosignal of these two epigenetic marks in young versus old wild-type mice and in the triple-transgenic mouse model of AD (3xTg-AD). The results show a decline in global 5-methylcytosine mark over time in all studied brain regions concomitant with a significant and widespread increase in 5-hydroxymethylcytosine mark in the aged transgenic mice in contrast to the age-matched controls. These differences in the methylation pattern of brain DNA in the 3xTg-AD that accumulates along age indicates abnormal formation of permissive chromatin structure associated with the increase in AD-related markers.
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Carla
authors.initials: C
authors.lastname: Cadena-del-Castillo
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Christian
authors.initials: C
authors.lastname: Valdes-Quezada
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carmona-Aldana
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Clorinda
authors.initials: C
authors.lastname: Arias
authors.affiliation: Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Federico
authors.initials: F
authors.lastname: Bermúdez-Rattoni
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000367:Age Factors; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 3xTg-AD; 5-hydroxymethylcytosine; Aging; Alzheimer's disease; DNA methylation; chromatin