Giuseppe Cibelli

Regulation of life and death by the zinc finger transcription factor Egr‐1

The biosynthesis of the zinc finger transcription factor Egr‐1 is stimulated by many extracellular signaling molecules including hormones, neurotransmitters, growth and differentiation factors, and cytotoxic metabolites. The 5′‐flanking region of the Egr‐1 gene contains genetic elements that are essential in connecting stimulation of the cells with enhanced transcription of the Egr‐1 gene, and subsequently, transcription of Egr‐1‐responsive genes. Thus, Egr‐1 links cellular signaling cascades with changes in the gene expression pattern. Many biological functions have been attributed to Egr‐1. Here, we discuss evidence for Egr‐1 control of cellular proliferation and programmed cell death. J. Cell. Physiol. 193: 287–292, 2002.

Radiofrequency radiation (900 MHz) induces Egr-1 gene expression and affects cell-cycle control in human neuroblastoma cells

Many environmental signals, including ionizing radiation and UV rays, induce activation of Egr‐1 gene, thus affecting cell growth and apoptosis. The paucity and the controversial knowledge about the effect of electromagnetic fields (EMF) exposure of nerve cells prompted us to investigate the bioeffects of radiofrequency (RF) radiation on SH‐SY5Y neuroblastoma cells. The effect of a modulated RF field of 900 MHz, generated by a wire patch cell (WPC) antenna exposure system on Egr‐1 gene expression, was studied as a function of time. Short‐term exposures induced a transient increase in Egr‐1 mRNA level paralleled with activation of the MAPK subtypes ERK1/2 and SAPK/JNK. The effects of RF radiations on cell growth rate and apoptosis were also studied. Exposure to RF radiation had an anti‐proliferative activity in SH‐SY5Y cells with a significant effect observed at 24 h. RF radiation impaired cell cycle progression, reaching a significant G2‐M arrest. In addition, the appearance of the sub‐G1 peak, a hallmark of apoptosis, was highlighted after a 24‐h exposure, together with a significant decrease in mRNA levels of Bcl‐2 and survivin genes, both interfering with signaling between G2‐M arrest and apoptosis. Our results provide evidence that exposure to a 900 MHz‐modulated RF radiation affect both Egr‐1 gene expression and cell regulatory functions, involving apoptosis inhibitors like Bcl‐2 and survivin, thus providing important insights into a potentially broad mechanism for controlling in vitro cell viability. J. Cell. Physiol. 213:759–767.

Corticotropin-releasing factor triggers neurite outgrowth of a catecholaminergic immortalized neuron via cAMP and MAP kinase signalling pathways.

Corticotropin‐releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress‐induced release of corticotropin (ACTH), β‐endorphin and other proopiomelanocortin‐derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus‐derived neurons. CRF triggers morphological changes in CATH.a cells including the appearence of extended long, slender neurites with prominent growth cones. CRF‐treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF‐induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP‐dependent protein kinase or extracellular signal‐regulated protein kinase (ERK), a subtype of the mitogen‐activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription‐based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.

Visuo-attentional and sensorimotor alpha rhythms are related to visuo-motor performance in athletes

This study tested the two following hypotheses: (i) compared with non‐athletes, elite athletes are characterized by a reduced cortical activation during the preparation of precise visuo‐motor performance; (ii) in elite athletes, an optimal visuo‐motor performance is related to a low cortical activation. To this aim, electroencephalographic (EEG; 56 channels; Be Plus EB‐Neuro) data were recorded in 18 right‐handed elite air pistol shooters and 10 right‐handed non‐athletes. All subjects performed 120 shots. The EEG data were spatially enhanced by surface Laplacian estimation. With reference to a baseline period, power decrease/increase of alpha rhythms during the preshot period indexed the cortical activation/deactivation (event‐related desynchronization/synchronization, ERD/ERS). Regarding the hypothesis (i), low‐ (about 8–10 Hz) and high‐frequency (about 10–12 Hz) alpha ERD was lower in amplitude in the elite athletes than in the non‐athletes over the whole scalp. Regarding the hypothesis (ii), the elite athletes showed high‐frequency alpha ERS (about 10–12 Hz) larger in amplitude for high score shots (50%) than for low score shots; this was true in right parietal and left central areas. A control analysis confirmed these results with another indicator of cortical activation (beta ERD, about 20 Hz). The control analysis also showed that the amplitude reduction of alpha ERD for the high compared with low score shots was not observed in the non‐athletes. The present findings globally suggest that in elite athletes (experts), visuo‐motor performance is related to a global decrease of cortical activity, as a possible index of spatially selective cortical processes (“neural efficiency”). Hum Brain Mapp, 2009.

Stress-related hormonal and psychological changes to official youth Taekwondo competitions

The aim of this study was to evaluate the effects of an official Taekwondo competition on the heart rate (HR), salivary α‐amylase (sA‐A), salivary free cortisol (sC), and Profile of Mood States (POMS) in 10 young male (14±0 years) and six female (13±1 years) athletes. POMS and hormones were measured 15 min before and directly after the competition. During the recovery phase (30 and 90 min), sA‐A and sC were also measured. HR measured during the competition was expressed as a percentage of individuals maximal heart rate (%HRmax) to evaluate the intensity of exercise. During the competition, athletes spent 65% of the time working at HR>90% of individuals HRmax. A significant increase (P<0.0001) in sA‐A (115%) was observed at the end of the match. At 30 min of recovery, sA‐A returned to the pre‐competition level. The peak sC values were observed at 30 min of recovery (P<0.001), returning to the pre‐competition level at 90 min of recovery. A gender difference (P=0.01) emerged only for sC, although a similar trend was observed for female and male athletes. Significantly higher post‐match scores emerged for Anger‐hostility (pre: 6.1±1.1, post: 11.2±1.9; P=0.03) and Depression‐dejection (pre: 4.5±0.5, post: 10.2±1.9; P=0.006), whereas the reverse picture was observed for Vigour‐activity (pre: 23.2±1.2, post: 16.3±1.7; P=0.0006). Taekwondo competition results in temporary changes in the stress‐related parameters measured in this study. The present findings suggest that this experimental paradigm can represent a useful model for further research on the effects of various stressors (i.e., training and competition) in Taekwondo athletes of different levels (i.e., novice, international).

Cortical sources of resting-state alpha rhythms are abnormal in persistent vegetative state patients.

OBJECTIVE High power of pre-stimulus cortical alpha rhythms (about 8-12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment. METHODS Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning--LCF score: I-II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I-II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III-IV), and 12 subjects who recovered (REC patients; follow-up LCF: V-VIII). RESULTS Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients. CONCLUSIONS These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state. SIGNIFICANCE Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Mobile phone emission modulates inter-hemispheric functional coupling of EEG alpha rhythms in elderly compared to young subjects

OBJECTIVE It has been reported that GSM electromagnetic fields (GSM-EMFs) of mobile phones modulate--after a prolonged exposure--inter-hemispheric synchronization of temporal and frontal resting electroencephalographic (EEG) rhythms in normal young subjects [Vecchio et al., 2007]. Here we tested the hypothesis that this effect can vary on physiological aging as a sign of changes in the functional organization of cortical neural synchronization. METHODS Eyes-closed resting EEG data were recorded in 16 healthy elderly subjects and 5 young subjects in the two conditions of the previous reference study. The GSM device was turned on (45 min) in one condition and was turned off (45 min) in the other condition. Spectral coherence evaluated the inter-hemispheric synchronization of EEG rhythms at the following bands: delta (about 2-4 Hz), theta (about 4-6 Hz), alpha 1 (about 6-8 Hz), alpha 2 (about 8-10 Hz), and alpha 3 (about 10-12 Hz). The aging effects were investigated comparing the inter-hemispheric EEG coherence in the elderly subjects vs. a young group formed by 15 young subjects (10 young subjects of the reference study; Vecchio et al., 2007). RESULTS Compared with the young subjects, the elderly subjects showed a statistically significant (p<0.001) increment of the inter-hemispheric coherence of frontal and temporal alpha rhythms (about 8-12 Hz) during the GSM condition. CONCLUSIONS These results suggest that GSM-EMFs of a mobile phone affect inter-hemispheric synchronization of the dominant (alpha) EEG rhythms as a function of the physiological aging. SIGNIFICANCE This study provides further evidence that physiological aging is related to changes in the functional organization of cortical neural synchronization.

Enhanced parasympathetic activity of sportive women is paradoxically associated to enhanced resting energy expenditure

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure.

Resting state cortical rhythms in athletes: A high-resolution EEG study

The present electroencephalographic (EEG) study tested the working hypothesis that the amplitude of resting state cortical EEG rhythms (especially alpha, 8-12 Hz) was higher in elite athletes compared with amateur athletes and non-athletes, as a reflection of the efficiency of underlying back-ground neural synchronization mechanisms. Eyes closed resting state EEG data were recorded in 16 elite karate athletes, 20 amateur karate athletes, and 25 non-athletes. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that the amplitude of parietal and occipital alpha 1 sources was significantly higher in the elite karate athletes than in the non-athletes and karate amateur athletes. Similar results were observed in parietal and occipital delta sources as well as in occipital theta sources. Finally, a control confirmatory experiment showed that the amplitude of parietal and occipital delta and alpha 1 sources was stronger in 8 elite rhythmic gymnasts compared with 14 non-athletes. These results supported the hypothesis that cortical neural synchronization at the basis of eyes-closed resting state EEG rhythms is enhanced in elite athletes than in control subjects.

Effects of simulated firefighting on the responses of salivary cortisol, alpha-amylase and psychological variables

The aim of this study was to evaluate the effects of a simulated firefighting intervention on salivary alpha-amylase (sA-A), free cortisol (sC), anxiety (STAI), and profile of mood states (POMS) in 20 male firefighters (age 32 ± 1 years, [Vdot]O 2peak: 43 ± 5 ml/kg per min). During the 12-min firefighting intervention (ambient temperature: 13 ± 1°C; relative humidity: 63 ± 1%), individuals spent 63 ± 28% of the time working at heart rate (HR) >85% of individual HRmax, [La] peak 9.2 ± 2.9 mM and ratings of perceived exertion 16 ± 2. At 30 min post-intervention significant (p < 0.001) increases in sA-A (174%) and sC (109%) were found with regard to values recorded before and after 90 min of the firefighting intervention. Since no differences emerged between pre-intervention and post intervention for STAI and POMS values, the hormonal changes were attributable to the intense physical stress of the simulated intervention. Further research is needed during real firefighting activities, where high emotional stress may also be present.