Chlorogenic Acid Prevents AMPA-Mediated Excitotoxicity in Optic Nerve Oligodendrocytes Through a PKC and Caspase-Dependent Pathways

In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities. Chlorogenic acid (CGA) has been demonstrated to possess potent neuroprotective activities against oxidative stress in various cellular models and pathological conditions. Hence, CGA protect against oxidative stress and excitotoxic insults mediated by AMPA receptors and that the protective mechanisms involve free radical scavenging, Ca²⁺ handling in the cytosol, and modulating antioxidant enzyme system. CGA was associated with the protein kinase A (PKC) signaling pathways transduction. Caspases and calpains have been studied as apoptotic mediators and cell death in this model of AMPA toxicity. Inhibitors of caspases initiators, caspases 1, 8, and 9, the upstream of caspase 3 effectors, have totally abrogated the protective activity of CGA. Inhibitors of calpains also totally abrogated the protective activity of CGA. In addition, a potential role for the CGA in inhibiting Bax in oligodendrocyte cell model undergoing AMPA is inducing excitotoxic death. Our results indicate that CGA exhibits a protective potential via antioxidant and apoptosis caspases and calpains dependent against AMPA-mediated excitotoxicity, and these finding indicate that CGA is able to be a good candidate for preventive approach for neurodegenerative disorders associated with loss and damage in oligodendrocytes and AMPA-mediated excitotoxicity.     

Recreational soccer training improves heart-rate variability indices and physical performance in untrained healthy adolescent

The aim of this study was to evaluate the effects of soccer training on short-term heart-rate variability, blood pressure, and physical fitness in untrained healthy adolescents. Twenty-two adolescent boys took part in this study: 11 boys were randomly assigned to participate in an 8-week soccer training and 11 boys served as a control group. Soccer exhibited significant increases in high-frequency power (difference 52.9%, P = 0.03, effect size: ES = 1.2), root mean squared of the standard deviation rMSSD (10.8%, P = 0.02, ES = 1), and a significant decrease in sympathetic activity LF (26.3%, P = 0.004, ES = 1.4). The control group showed an increase in rMSSD (9.4%, P = 0.05, ES = 1). The soccer group showed increases in estimated aerobic fitness (30.9%, P = 0.001, ES = 1.50) and 20-m sprint performance (4.1%, P = 0.004, ES = 0.8) with a trend to an improvement in horizontal jumping (3.8%, P = 0.15, ES = 0.8). In conclusion, soccer-based training improved measures of both physical fitness and autonomic function making soccer an effective training strategy for improving health-related fitness measures in untrained adolescents.     

The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors

Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellular concentrations of Na⁺ and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3–10 mM glutamate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR‐excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO‐treated compared with saline treated rats. Taken together our data demonstrate that the conversion of glutamate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2017;65:401–415     

Oxidative stress in patients with asthma and its relation to uncontrolled asthma

This study aims to evaluate markers of oxidative stress in Tunisian asthmatic patients and investigate whether their markers are correlated with uncontrolled asthma.This prospective cohort study was conducted on 48 healthy subjects and 60 patients with asthma (34 patients with controlled asthma and 26 patients with uncontrolled asthma). The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in plasma by spectrophotometry.Asthmatic patients have significantly higher plasmatic levels of MDA and AOPP than healthy controls (p < 0.001). Lower GSH level and GPx activity were found in patients with asthma compared to controls (p < 0.001). In contrast, higher SOD activity was noted in asthmatic patients (p < 0.001).The comparison among the patients with controlled asthma and uncontrolled asthma revealed increased MDA and AOPP levels and SOD activity (p < 0.001) as well as a decreased GSH level and GPx activity (p = 0.004, p = 0.019) in patients with uncontrolled asthma. Spirometry level was significantly correlated with SOD activity (r = 0.447; p = 0.010), whereas no significant correlations were found with the other parameters (MDA, AOPP, GSH, and GPx).Asthmatic patients, especially those with uncontrolled asthma, suffer a high degree of reactive oxygen species (ROS) formation causing considerable oxidative stress. Increased MDA level and SOD activity and reduced GPx activity were predictors of poorly controlled asthma.     

Une cause inhabituelle d’hypertension artérielle

Secondary hypertension is relatively rare. Its etiologies are essentially renal or endocrine. The adrenocortical carcinoma, a rare malignant tumor, is one of the most exceptional causes of hypertension. We report the case of a young woman presenting with hypertension and ascites of great abundance. She had hypokalemia, hepatic cytolysis and cholestasis. Thoracic, abdominal and pelvic CT scans showed adrenal mass, liver and lung nodules, osteolytic lesions of the sacrum. The biopsy of liver nodules confirmed the diagnosis of a metastatic malignant adrenocortical carcinoma. The hormonal investigations revealed cortisol and testosterone hypersecretion. The evolution was quickly fatal, the patient passed out a few days after her hospitalization.