Short Communication Extremely low-frequency electromagnetic fields activate the antioxidant pathway Nrf2 in a Huntington’s disease-like rat model Inmaculada Tasset a,1 , Aleyda Pérez-Herrera b,1 , Francisco J. Medina a , Óscar Arias-Carrión c , René Drucker-Colín d , Isaac Túnez a, * a Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Universidad de Córdoba, Córdoba, Spain b Unidad de Investigación de Lípidos y Aterosclerosis, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Córdoba, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain c Department of Neurology, Technical University Munich, Munich, Germany d Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), México D.F., Mexico article info Article history: Received 3 November 2011 Received in revised form 18 March 2012 Accepted 21 March 2012 Available online 24 April 2012 Keywords: Antioxidants Nrf2 Neurodegenerative disease Oxidative stress Transcranial magnitc stimulation abstract Transcranial magnetic stimulation (TMS) is a non-invasive technique used recently to treat different neuropsychiatric and neurodegenerative disorders. Despite its proven value, the mechanisms through which TMS exerts its beneficial action on neuronal function remain unclear. Recent studies have shown that its beneficial effects may be at least partly due to a neuroprotective effect on oxidative and cell damage. This study shows that TMS can modulate the Nrf2 transcriptor factor in a Huntington’s disease- like rat model induced by 3-nitropropionic acid (3-NP). Western blot analysis demonstrated that 3-NP caused a reduction in Nrf2 in both cytoplasm and nucleus, while TMS applied to 3-NP-treated rats triggered an increase in cytoplasm and nucleus Nrf2 levels. It was therefore concluded that TMS modulates Nrf2 expression and translocation and that these mechanisms may partly explain the neu- roprotective effect of TMS, as well as its antioxidant and cell protection capacity. Ó 2013 Elsevier Inc. All rights reserved. Introduction To neutralize the detrimental effect of reactive oxygen species (ROS), mammalian cells have evolved a hierarchy of sophisticated antioxidant response mechanism regulated by NF-E2-related factor 2 (Nrf2) transcription factor [1,6,9,10]. Nrf2 has been highly impli- cated in up-regulation of g-glutamyl-cysteine ligase (GCL), the enzyme that catalyses the rate-limiting step in glutathione synthesis [3], and thus up-regulation GSH levels. 3-nitropropionic acid (3-NP) is a neurotoxin which is an inhib- itor of succinate dehydrogenase enzyme. This toxin causes an experimental model with changes similar to those occurring in Huntington’s disease (HD) [7]. Recently, it has been demonstrated the therapeutic potential of repetitive transcranial magnetic stimulation (application of different consecutive pulses) in degenerative disorders. Nevertheless, its cellular mechanisms are only beginning to be understood. Different studies reported, however, that extremely low-frequency electro- magnetic fields (ELFEFs) stimulation has a beneficial effect on oxidative stress [11], as well as modulating the expression of different genes [7]. This study aimed to determine whether ELFEF is capable of inducing Nrf2 nuclear translocation in an animal model of HD. Material and methods Two month-old male Wistar rats weighing between 190 and 200 g at beginning study were purchased from Charles River (Barcelona, Spain). These animals were divided into three groups (n ¼ 4 animals per group) as follows: i) control, ii) 3-NP-treated rats (20 mg/i.p./kg BW, in saline pH 7.4; SigmaeAldrich, St. Louis, MO, USA), for 4 consecutive days (as previously reported [11], and iii) 3- NP-treated rats plus ELFEF (3-NPþ ELFEF). Control and 3-NP group involved placing the animals in the same magnetic stimulation apparatus, plastic cylindrical cage, for the same period of time, but without any actual stimulation; no oscillatory magnetic field. Animals were treated in agreement with the European Communi- ties Council Directive of 24 November 1986 (86/609/ECC) and the AP-H has a Grant of Consejo Nacional de Ciencia y Tecnología (CONACYT), México. The authors declare that they have not any conflict of interest. * Corresponding author. Tel.: þ34 957218268; fax: þ34 957218229. E-mail address: fm2tufii@uco.es (I. Túnez). 1 Equal contribution. Contents lists available at SciVerse ScienceDirect Brain Stimulation journal homepage: www.brainstimjrnl.com 1935-861X/$ e see front matter Ó 2013 Elsevier Inc. All rights reserved. doi:10.1016/j.brs.2012.03.015 Brain Stimulation 6 (2013) 84e86