Claudia Consales

Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.

Exposure to Perfluoroalkyl Substances and Sperm DNA Global Methylation in Arctic and European Populations

Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non‐occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE‐1, Satα) quantified by PCR‐pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5‐methyl‐cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo‐ and hyper‐methylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. Environ. Mol. Mutagen. 55:591–600, 2014.

S-Nitrosoglutathione Reductase Plays Opposite Roles in SH-SY5Y Models of Parkinson’s Disease and Amyotrophic Lateral Sclerosis

Oxidative and nitrosative stresses have been reported as detrimental phenomena concurring to the onset of several neurodegenerative diseases. Here we reported that the ectopic modulation of the denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR) differently impinges on the phenotype of two SH-SY5Y-based in vitro models of neurodegeneration, namely, Parkinsons disease (PD) and familial amyotrophic lateral sclerosis (fALS). In particular, we provide evidence that GSNOR-knocking down protects SH-SY5Y against PD toxins, while, by contrast, its upregulation is required for G93A-SOD1 expressing cells resistance to NO-releasing drugs. Although completely opposite, both conditions are characterized by Nrf2 localization in the nuclear compartment: in the first case induced by GSNOR silencing, while in the second one underlying the antinitrosative response. Overall, our results demonstrate that GSNOR expression has different effect on neuronal viability in dependence on the stimulus applied and suggest that GSNOR could be a responsive gene downstream of Nrf2 activation.

Indices of methylation in sperm DNA from fertile men differ between distinct geographical regions

STUDY QUESTION Which are the main determinants, if any, of sperm DNA methylation levels? SUMMARY ANSWER Geographical region resulted associated with the sperm methylation status assessed on genome-wide repetitive sequences. WHAT IS KNOWN ALREADY DNA methylation level, assessed on repetitive sequences from peripheral blood lymphocyte, can vary with age, gender, alcohol consumption and white blood cell counts. STUDY DESIGN, SIZE, DURATION A cross-sectional study. Individual data were collected from 269 young healthy men of proven fertility living in three geographical regions: Inuits from Greenland, Caucasians from Warsaw (Poland) and Kharkiv (Ukraine). Semen samples were collected between May 2002 and February 2004 and aliquots were immediately frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS We estimated sperm DNA global methylation level (DGML) in two ways. First DNA methylation in repetitive DNA sequences (LINE-1, Satα and Alu) was quantified by PCR pyrosequencing after bisulfite conversion and second by flow cytometry (FCM) using fluorescently labeled monoclonal antibodies anti-5-methylcytosine. We analyzed whether personal characteristics and habits, body mass index, semen quality parameters, sperm chromatin integrity, biomarkers of accessory gland function and the plasma concentration of reproductive hormones were associated with sperm DNA methylation levels in men. Associations were evaluated by analysis of variance and linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE The geographical location emerged as the main determinant when using the methylation level in repetitive sequences. FCM DGML results were not associated with those from repetitive sequence analysis. No other consistent associations between methylation markers and the assessed variables were identified across countries. LIMITATIONS, REASONS FOR CAUTION The methods used are only surrogates of the actual sperm methylome and the methylation levels at individual specific loci were not explored. WIDER IMPLICATIONS OF THE FINDINGS Sperm DGML is relatively independent from semen quality parameters and is a new candidate biomarker for epidemiological studies of the impact of environmental contaminants on male fertility. STUDY FUNDING/COMPETING INTERESTS The study is part of the project CLEAR (Climate change, Environmental contaminants and Reproductive health) supported by the European Commission 7th framework program, contract no: FP7-ENV-2008-1-226217. No competing interest is declared.

A Microdosimetric Study of Electropulsation on Multiple Realistically Shaped Cells: Effect of Neighbours

Over the past decades, the effects of ultrashort-pulsed electric fields have been used to investigate their action in many medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). Promising aspects of these pulses has led to several in vitro and in vivo experiments to clarify their action. Since the basic mechanisms of these pulses have not yet been fully clarified, scientific interest has focused on the development of numerical models at different levels of complexity: atomic (molecular dynamic simulations), microscopic (microdosimetry) and macroscopic (dosimetry). The aim of this work is to demonstrate that, in order to predict results at the cellular level, an accurate microdosimetry model is needed using a realistic cell shape, and with their position and packaging (cell density) characterised inside the medium.

The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview: Epigenetic Response to DBS and TMS

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non-coding RNAs expression, have been recently included among the key determinants contributing to Parkinsons Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic-based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3-14, 2018.

A microdosimetry study for a realistic shaped nucleus

In the last decades, the effects of ultrashort pulsed electric fields have been investigated demonstrating their capability to be involved in a great number of medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). In particular, experiments in literature demonstrate that internal structures can be involved when pulse duration is reduced. Up to now, the mechanism that permits the electroporation phenomenon has not been completely understood and hence atomistic, microdosimetry and dosimetry models have been developed to help in this field. Aim of this work is to demonstrate the importance of realistically model also the internal organelles to obtain predictive results of effects at sub-cellular level with a microdosimetry model.

A proposed integrated systems approach to the radiation biology of cosmic interest: biophysics and molecular characterization of tissues irradiated with 14 MeV neutrons

Low-dose exposure of ionizing radiation triggers cell-to-cell communications and tissue interplay alterations. These alterations may play a fundamental role in non-cancer effects, overwhelming the theory of the DNA centric approach. Neither the mechanisms of these effects are fully understood nor is it possible to dissect the real incidence of quality and quantity of incident radiation during in vivo exposure, overall for particulate high-linear energy transfer (LET) radiation. Moreover, the knowledge of particulate high-LET radiation is mandatory for the human deep space exploration and to gain efficiency in the dose/effect ratio for radiotherapy. The aim of this mini-review was to describe an integrated system approach to the radiation biology of cosmic interest which could be set up in the framework of a future Sino-Italy cooperation among participating laboratories. We propose, in particular, to deliver X-rays and neutron irradiation at ENEA-FNG (Frascati, Italy) and heavy ion irradiation at IMP-CAS (Lanzhou, China) to in vivo models. The integrated system approach will focus on the correlation between the quality and quantity of radiation exposure and its in vivo biological effects. Wide range molecular profiling will analyze mainly cell and DNA damages and cell-to-cell and tissues interplay, meanwhile biochemical and chemical specific composition will be detected by infrared spectroscopy. The recently characterized alteration of leptin metabolism is discussed in more detail to present a successful example of systemic approach to cosmic radiation biology.