Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.

Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation. Female mice received a single 4 Gy whole-brain radiation dose on postnatal day (PND) 21 and were randomized to 0.24% Li2CO3 chow or normal chow from PND 49 to 77. Hippocampal neurogenesis was assessed on PND 77, 91, and 105. We found that lithium treatment had a pro-proliferative effect on neural progenitors, but neuronal integration occurred only after it was discontinued. Also, the treatment ameliorated deficits in spatial learning and memory retention observed in irradiated mice. Gene expression profiling and DNA methylation analysis identified two novel factors related to the observed effects, Tppp, associated with microtubule stabilization, and GAD2/65, associated with neuronal signaling. Our results show that lithium treatment reverses irradiation-induced loss of hippocampal neurogenesis and cognitive impairment even when introduced long after the injury. We propose that lithium treatment should be intermittent in order to first make neural progenitors proliferate and then, upon discontinuation, allow them to differentiate. Our findings suggest that pharmacological treatment of cognitive so-called late effects in childhood cancer survivors is possible.

Correction to: Can Neonatal Systemic Inflammation and Hypoxia Yield a Cerebral Palsy-Like Phenotype in Periadolescent Mice?

The original version of this article unfortunately contained a mistake in Author name. In Rochellys Diaz Heijtz, "Diaz" should be classified as Familyname.

Can Neonatal Systemic Inflammation and Hypoxia Yield a Cerebral Palsy-Like Phenotype in Periadolescent Mice?

Cerebral palsy (CP) is one of the most common childhood-onset motor disabilities, attributed to injuries of the immature brain in the foetal or early postnatal period. The underlying mechanisms are poorly understood, rendering prevention and treatment strategies challenging. The aim of the present study was to establish a mouse model of CP for preclinical assessment of new interventions. For this purpose, we explored the impact of a double neonatal insult (i.e. systemic inflammation combined with hypoxia) on behavioural and cellular outcomes relevant to CP during the prepubertal to adolescent period of mice. Pups were subjected to intraperitoneal lipopolysaccharide (LPS) injections from postnatal day (P) 3 to P6 followed by hypoxia at P7. Gene expression analysis at P6 revealed a strong inflammatory response in a brain region-dependent manner. A comprehensive battery of behavioural assessments performed between P24 and P47 showed impaired limb placement and coordination when walking on a horizontal ladder in both males and females. Exposed males also displayed impaired performance on a forelimb skilled reaching task, altered gait pattern and increased exploratory activity. Exposed females showed a reduction in grip strength and traits of anxiety-like behaviour. These behavioural alterations were not associated with gross morphological changes, white matter lesions or chronic inflammation in the brain. Our results indicate that the neonatal double-hit with LPS and hypoxia can induce subtle long-lasting deficits in motor learning and fine motor skills, which partly reflect the symptoms of children with CP who have mild gross and fine motor impairments.

Hippocampal lipidome and transcriptome profile alterations triggered by acute exposure of mice to GSM 1800 MHz mobile phone radiation: An exploratory study.

BACKGROUND: The widespread use of wireless devices during the last decades is raising concerns about adverse health effects of the radiofrequency electromagnetic radiation (RF-EMR) emitted from these devices. Recent research is focusing on unraveling the underlying mechanisms of RF-EMR and potential cellular targets. The "omics" high-throughput approaches are powerful tools to investigate the global effects of RF-EMR on cellular physiology. METHODS: In this work, C57BL/6 adult male mice were whole-body exposed (nExp  = 8) for 2 hr to GSM 1800 MHz mobile phone radiation at an average electric field intensity range of 4.3-17.5 V/m or sham-exposed (nSE  = 8), and the RF-EMR effects on the hippocampal lipidome and transcriptome profiles were assessed 6 hr later. RESULTS: The data analysis of the phospholipid fatty acid residues revealed that the levels of four fatty acids [16:0, 16:1 (6c + 7c), 18:1 9c, eicosapentaenoic acid omega-3 (EPA, 20:5 ω3)] and the two fatty acid sums of saturated and monounsaturated fatty acids (SFA and MUFA) were significantly altered (p < 0.05) in the exposed group. The observed changes indicate a membrane remodeling response of the tissue phospholipids after nonionizing radiation exposure, reducing SFA and EPA, while increasing MUFA residues. The microarray data analysis demonstrated that the expression of 178 genes changed significantly (p < 0.05) between the two groups, revealing an impact on genes involved in critical biological processes, such as cell cycle, DNA replication and repair, cell death, cell signaling, nervous system development and function, immune system response, lipid metabolism, and carcinogenesis. CONCLUSIONS: This study provides preliminary evidence that mobile phone radiation induces hippocampal lipidome and transcriptome changes that may explain the brain proteome changes and memory deficits previously shown by our group.

Applying Broadband Dielectric Spectroscopy (BDS) for the Biophysical Characterization of Mammalian Tissues under a Variety of Cellular Stresses.

The dielectric properties of biological tissues can contribute non-invasively to a better characterization and understanding of the structural properties and physiology of living organisms. The question we asked, is whether these induced changes are effected by an endogenous or exogenous cellular stress, and can they be detected non-invasively in the form of a dielectric response, e.g., an AC conductivity switch in the broadband frequency spectrum. This study constitutes the first methodological approach for the detection of environmental stress-induced damage in mammalian tissues by the means of broadband dielectric spectroscopy (BDS) at the frequencies of 1-106 Hz. Firstly, we used non-ionizing (NIR) and ionizing radiation (IR) as a typical environmental stress. Specifically, rats were exposed to either digital enhanced cordless telecommunication (DECT) radio frequency electromagnetic radiation or to γ-radiation, respectively. The other type of stress, characterized usually by high genomic instability, was the pathophysiological state of human cancer (lung and prostate). Analyzing the results of isothermal dielectric measurements provided information on the tissues' water fraction. In most cases, our methodology proved sufficient in detecting structural changes, especially in the case of IR and malignancy. Useful specific dielectric response patterns are detected and correlated with each type of stress. Our results point towards the development of a dielectric-based methodology for better understanding and, in a relatively invasive way, the biological and structural changes effected by radiation and developing lung or prostate cancer often associated with genomic instability.

Mobile-phone radiation-induced perturbation of gene-expression profiling, redox equilibrium and sporadic-apoptosis control in the ovary of Drosophila melanogaster.

The daily use by people of wireless communication devices has increased exponentially in the last decade, begetting concerns regarding its potential health hazards. Drosophila melanogaster four days-old adult female flies were exposed for 30 min to radiation emitted by a commercial mobile phone at a SAR of 0.15 W/kg and a SAE of 270 J/kg. ROS levels and apoptotic follicles were assayed in parallel with a genome-wide microarrays analysis. ROS cellular contents were found to increase by 1.6-fold (x), immediately after the end of exposure, in follicles of pre-choriogenic stages (germarium - stage 10), while sporadically generated apoptotic follicles (germarium 2b and stages 7-9) presented with an averaged 2x upregulation in their sub-population mass, 4 h after fly's irradiation with mobile device. Microarray analysis revealed 168 genes being differentially expressed, 2 h post-exposure, in response to radiofrequency (RF) electromagnetic field-radiation exposure (≥1.25x, P < 0.05) and associated with multiple and critical biological processes, such as basic metabolism and cellular subroutines related to stress response and apoptotic death. Exposure of adult flies to mobile-phone radiation for 30 min has an immediate impact on ROS production in animal's ovary, which seems to cause a global, systemic and non-targeted transcriptional reprogramming of gene expression, 2 h post-exposure, being finally followed by induction of apoptosis 4 h after the end of exposure. Conclusively, this unique type of pulsed radiation, mainly being derived from daily used mobile phones, seems capable of mobilizing critical cytopathic mechanisms, and altering fundamental genetic programs and networks in D. melanogaster.

Immune responses of a wall lizard to whole-body exposure to radiofrequency electromagnetic radiation.

PURPOSE: During the last three decades, the number of devices that emit non-ionizing electromagnetic radiation (EMR) at the wireless communication spectrum has rapidly increased and possible effects on living organisms have become a major concern. The purpose of this study was to investigate the effects of radiofrequency EMR emitted by a widely used wireless communication device, namely the Digital Enhanced Communication Telephony (DECT) base, on the immune responses of the Aegean wall lizard (Podarcis erhardii). MATERIALS AND METHODS: Adult male lizards were exposed 24 h/day for 8 weeks to 1880-1900 MHz DECT base radiation at average electric field intensity of 3.2 V/m. Immune reactivity was assessed using the phytohemagglutinin (PHA) skin swelling and mixed lymphocyte reaction (MLR) tests. RESULTS: Our results revealed a noticeable suppression (approximately 45%) of inflammatory responses in EMR-exposed lizards compared to sham-exposed animals. T cell-mediated responses were marginally affected. CONCLUSION: Daily radiofrequency EMR exposure seems to affect, at least partially, the immunocompetence of the Aegean wall lizard.

Response of Caenorhabditis elegans to wireless devices radiation exposure.

PURPOSE: To examine the impact of electromagnetic radiation, produced by GSM (Global System for Mobile communications) mobile phones, Wi-Fi (Wireless-Fidelity) routers and wireless DECT (Digital Enhanced Cordless Telecommunications) phones, on the nematode Caenorhabditis elegans. MATERIALS AND METHODS: We exposed synchronized populations, of different developmental stages, to these wireless devices at E-field levels below ICNIRP's (International Commission on Non-Ionizing Radiation Protection) guidelines for various lengths of time. WT (wild-type) and aging- or stress-sensitive mutant worms were examined for changes in growth, fertility, lifespan, chemotaxis, short-term memory, increased ROS (Reactive Oxygen Species) production and apoptosis by using fluorescent marker genes or qRT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction). RESULTS: No statistically significant differences were found between the exposed and the sham/control animals in any of the experiments concerning lifespan, fertility, growth, memory, ROS, apoptosis or gene expression. CONCLUSIONS: The worm appears to be robust to this form of (pulsed) radiation, at least under the exposure conditions used.

Brain proteome response following whole body exposure of mice to mobile phone or wireless DECT base radiation.

The objective of this study was to investigate the effects of two sources of electromagnetic fields (EMFs) on the proteome of cerebellum, hippocampus, and frontal lobe in Balb/c mice following long-term whole body irradiation. Three equally divided groups of animals (6 animals/group) were used; the first group was exposed to a typical mobile phone, at a SAR level range of 0.17-0.37 W/kg for 3 h daily for 8 months, the second group was exposed to a wireless DECT base (Digital Enhanced Cordless Telecommunications/Telephone) at a SAR level range of 0.012-0.028 W/kg for 8 h/day also for 8 months and the third group comprised the sham-exposed animals. Comparative proteomics analysis revealed that long-term irradiation from both EMF sources altered significantly (p < 0.05) the expression of 143 proteins in total (as low as 0.003 fold downregulation up to 114 fold overexpression). Several neural function related proteins (i.e., Glial Fibrillary Acidic Protein (GFAP), Alpha-synuclein, Glia Maturation Factor beta (GMF), and apolipoprotein E (apoE)), heat shock proteins, and cytoskeletal proteins (i.e., Neurofilaments and tropomodulin) are included in this list as well as proteins of the brain metabolism (i.e., Aspartate aminotransferase, Glutamate dehydrogenase) to nearly all brain regions studied. Western blot analysis on selected proteins confirmed the proteomics data. The observed protein expression changes may be related to brain plasticity alterations, indicative of oxidative stress in the nervous system or involved in apoptosis and might potentially explain human health hazards reported so far, such as headaches, sleep disturbance, fatigue, memory deficits, and brain tumor long-term induction under similar exposure conditions.

Cranial and postcranial skeletal variations induced in mouse embryos by mobile phone radiation.

This study focuses on foetal development following mild daily exposure of pregnant mice to near field electromagnetic radiation emitted by a mobile phone. The investigation was motivated by the fact that the potentially hazardous electromagnetic radiation emitted by mobile phones is currently of tremendous public interest. Physically comparable pregnant mice were exposed to radiofrequency radiation GSM 900MHz emitted by a mobile phone. Within 5h after birth most cubs were fixed followed by double staining in toto, and conventional paraffin histology. Other cubs remained with their mothers until teeth eruption. Structural development was assessed by examining newborns for the presence of anomalies and/or variations in soft tissues and skeletal anatomy. Electromagnetic radiofrequency exposed newborns, externally examined, displayed a normal phenotype. Histochemical and histological studies, however, revealed variations in the exposed foetuses with respect to control ones concerning the ossification of cranial bones and thoracic cage ribs, as well as displacement of Meckelian cartilage. Littermates examined after teeth eruption displayed normal phenotypes. It is concluded that mild exposure to mobile phone radiation may affect, although transiently, mouse foetal development at the ossification level. The developmental variations observed could be explained by considering the different embryonic origin and mode of ossification of the affected skeletal elements.