CNP and DPYSL2 mRNA Expression and Promoter Methylation Levels in Brain of Alzheimer's Disease Patients

Article type: Research Article

Authors: Natalia Silva, Patrícia^a | Furuya, Tatiane Katsue^a | Sampaio Braga, Ianna^a | Rasmussen, Lucas Trevizani^c | de Labio, Roger Willian^c | Bertolucci, Paulo Henrique^b | Chen, Elizabeth Suchi^a | Turecki, Gustavo^d | Mechawar, Naguib^d | Payão, Spencer Luiz^{a; c} | Mill, Jonathan^e | Cardoso Smith, Marília^{a; *}

Affiliations: [a] Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil | [b] Disciplina de Neurologia Clínica, Departamento de Neurologia e Neurocirurgia (UNIFESP), São Paulo, SP, Brazil | [c] Laboratório de Genética, Hemocentro, Faculdade de Medicina de Marília (FAMEMA), Marília, SP, Brazil | [d] Psychiatry Department, Douglas Hospital Research Center, McGill University, Montreal, Canada | [e] Institute of Psychiatry, King's College, London, UK

Correspondence: [*] Correspondence to: Prof. Dr. Marília de Arruda Cardoso Smith, Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP/EPM, Rua Botucatu, 740, Edifício Leitño da Cunha, 1° andar, CEP 04023-900, São Paulo, SP, Brazil. Tel./Fax: +5511 5576 4260/+5511 5576 4264; E-mail: [email protected].

Abstract: Alzheimer's disease (AD) is a highly prevalent type of dementia in the elderly population. AD is a complex neurodegenerative disorder. Thus, epigenetic mechanisms that regulate gene expression might have an important role in AD. CNP (2′,3′-Cyclic Nucleotide 3′ Phosphodiesterase) gene encodes a protein used as an index of myelin alterations. DPYSL2 (Dihydropyrimidinase-like 2) is described as acting in structural and regulatory processes in the central nervous system, such as neural differentiation, neurotransmitter release, and stabilization of microtubules. In this study, we evaluated gene expression and epigenetic regulation of CNP and DPYSL2 genes in three postmortem brain regions (entorhinal and auditory cortices and hippocampus) of AD patients and healthy elderly controls. mRNA quantification was performed using qRT-PCR, and promoter DNA methylation patterns were determined by mass spectrometry using the Sequenom EpiTYPER platform. We observed CNP mRNA downregulation in entorhinal and auditory cortex in relation to the same regions of the control group. CNP alterations in the brain might suggest impairment in myelination leading to a synaptic and cognition loss. No AD-associated differences in CNP and DPYSL2 promoter DNA methylation were observed, suggesting that other mechanisms may be involved in mediating the observed CNP gene expression.

Keywords: CNP, DPYSL2, epigenetics, gene expression, mRNA

DOI: 10.3233/JAD-2012-121192

Journal: Journal of Alzheimer's Disease, vol. 33, no. 2, pp. 349-355, 2013